The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA
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{"title"=>"The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA", "type"=>"journal", "authors"=>[{"first_name"=>"Wan", "last_name"=>"Li", "scopus_author_id"=>"55521331200"}, {"first_name"=>"Qin", "last_name"=>"Yan", "scopus_author_id"=>"55808071589"}, {"first_name"=>"Xiangya", "last_name"=>"Ding", "scopus_author_id"=>"57189035068"}, {"first_name"=>"Chenyou", "last_name"=>"Shen", "scopus_author_id"=>"56096512300"}, {"first_name"=>"Minmin", "last_name"=>"Hu", "scopus_author_id"=>"56999160100"}, {"first_name"=>"Ying", "last_name"=>"Zhu", "scopus_author_id"=>"56349151400"}, {"first_name"=>"Di", "last_name"=>"Qin", "scopus_author_id"=>"8771702100"}, {"first_name"=>"Hongmei", "last_name"=>"Lu", "scopus_author_id"=>"57188949030"}, {"first_name"=>"Brian J.", "last_name"=>"Krueger", "scopus_author_id"=>"56257390500"}, {"first_name"=>"Rolf", "last_name"=>"Renne", "scopus_author_id"=>"7003589017"}, {"first_name"=>"Shou Jiang", "last_name"=>"Gao", "scopus_author_id"=>"7403257411"}, {"first_name"=>"Chun", "last_name"=>"Lu", "scopus_author_id"=>"55733530800"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"scopus"=>"2-s2.0-84964884515", "issn"=>"15537374", "pmid"=>"27128969", "sgr"=>"84964884515", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "doi"=>"10.1371/journal.ppat.1005605", "pui"=>"610216765"}, "id"=>"9ff45a10-fa9c-3911-a364-0817f583b207", "abstract"=>"Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a gammaherpesvirus etiologically associated with KS, a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells. KSHV encodes 25 mature microRNAs but their roles in KSHV-induced tumor dissemination and angiogenesis remain unknown. Here, we investigated KSHV-encoded miR-K12-6-3p (miR-K6-3p) promotion of endothelial cell migration and angiogenesis, which are the underlying mechanisms of tumor dissemination and angiogenesis. We found that ectopic expression of miR-K6-3p promoted endothelial cell migration and angiogenesis. Mass spectrometry, bioinformatics and luciferase reporter analyses revealed that miR-K6-3p directly targeted sequence in the 3' untranslated region (UTR) of SH3 domain binding glutamate-rich protein (SH3BGR). Overexpression of SH3BGR reversed miR-K6-3p induction of cell migration and angiogenesis. Mechanistically, miR-K6-3p downregulated SH3BGR, hence relieved STAT3 from SH3BGR direct binding and inhibition, which was required for miR-K6-3p maximum activation of STAT3 and induction of cell migration and angiogenesis. Finally, deletion of miR-K6 from the KSHV genome abrogated its effect on the SH3BGR/STAT3 pathway, and KSHV-induced migration and angiogenesis. Our results illustrated that, by inhibiting SH3BGR, miR-K6-3p enhances cell migration and angiogenesis by activating the STAT3 pathway, and thus contributes to the dissemination and angiogenesis of KSHV-induced malignancies.", "link"=>"http://www.mendeley.com/research/sh3bgrstat3-pathway-regulates-cell-migration-angiogenesis-induced-gammaherpesvirus-microrna", "reader_count"=>7, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/5032780"], "description"=>"<p><b>(A).</b> Western blotting analysis of SH3BGR, phosphorylated STAT3 and STAT3 in HUVEC transduced with lentivirus empty vector (<b>mpCDH</b>) or lentivirus-miR-K6-3p (<b>miR-K6-3p</b>), and HUVEC treated with PBS (<b>Mock</b>) or infected with KSHV (<b>KSHV</b>), respectively. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(B).</b> Western blotting analysis of phosphorylated STAT3 in HUVEC transduced with lentivirus-mediating empty vector (<b>mpCDH</b>) or miR-K6-3p (<b>miR-K6-3p</b>), which were subsequently co-transduced with lentivirus SH3BGR (<b>SH3BGR</b>) or its control pHAGE (<b>pHAGE</b>), respectively. The antibody against Flag-tag was used to detect the exogenous expression of SH3BGR. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(C).</b> The physiological interaction between SH3BGR and STAT3. HUVEC were transduced with lentivirus-SH3BGR (<b>SH3BGR</b>) or its control pHAGE (<b>pHAGE</b>) and subjected to co-immunoprecipitation with the antibody against SH3BGR (<b>IP: SH3BGR</b>) or STAT3 (<b>IP: STAT3</b>) followed by Western blotting using indicated antibodies (left panel). Or HUVEC were tranfected with pCMV3-Flag-STAT3 construct (<b>STAT3</b>) or its control pCMV3-C-Flag (<b>pCMV</b>) and subjected to co-immunoprecipitation with the antibody against SH3BGR (<b>IP: SH3BGR</b>) or STAT3 (<b>IP: STAT3</b>) followed by Western blotting using indicated antibodies (<b>right panel</b>). <b>(D).</b> Confocal microscopy for localization of SH3BGR and phosphorylated STAT3. HUVEC transduced with lentivirus SH3BGR (<b>SH3BGR</b>) and its control pHAGE (<b>pHAGE</b>), or lentivirus-mediated a mixture of short hairpin RNAs targeting SH3BGR (<b>shSH3BGR</b>) and its empty vector (<b>mpCDH</b>) were stained for SH3BGR (red) and p-STAT3 (green) with indicated antibodies. 4’, 6’-diamidino-2-phenylindole (DAPI) (blue) stains nuclei. <b>(E).</b> Association of SH3BGR with full-length STAT3 <i>in vitro</i>. GST or GST-STAT3 fusion protein was used to pull down purified 6 x His-SH3BGR protein. Proteins were eluted and SH3BGR bound to GST-STAT3 was detected by immunoblotting with anti-His antibody. Equal loading of purified GST-STAT3 and 6 x His-SH3BGR were detected by immunoblotting with anti-GST antibody (middle panel) and anti-His antibody (bottom panel), respectively.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206401, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_interaction_between_SH3BGR_and_STAT3_in_endothelial_cells_/3206401", "title"=>"The interaction between SH3BGR and STAT3 in endothelial cells.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032783"], "description"=>"<p><b>(A)</b>. Western blotting analysis of phosphorylated STAT3 and VEGFA in HUVEC transduced with lentivirus-mediated empty vector (<b>mpCDH</b>) or miR-K6-3p (<b>miR-K6-3p</b>), and further transduced with lentivirus-mediated a mixture of short hairpin RNAs targeting STAT3 (<b>shSTAT3</b>). Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(B)</b>. Transwell migration assay for HUVEC treated as in (<b>A</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. (C). Microtubule formation assay for HUVEC treated as in (A). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(D)</b>. Western blotting analysis of phosphorylated STAT3, STAT3 and VEGFA in HUVEC transduced with lentivirus-mediated empty vector (<b>mpCDH</b>) or miR-K6-3p (<b>miR-K6-3p</b>) and further treated with the JAK2 inhibitor, AG490 (<b>AG490</b>) or its control (<b>DMSO</b>). Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(E)</b>. Transwell migration assay for HUVEC treated as in (<b>D</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(F)</b>. Microtubule formation assay for HUVEC treated as in (D). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(G)</b>. HUVEC treated as in (<b>A</b>) were examined for their proangiogenic effects in Matrigel plug assay in nude mice as described in the “Materials and Methods” section. The hemoglobin levels of the Matrigel plugs were determined with hemoglobin content calculated based on the standard curve. Data represent mean ± SD, each group with five tumors (n = 5). Three independent experiments were performed and similar results were obtained. <b>(H)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in the Matrigel plugs treated as in (G) were determined by qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <i>n</i>.<i>s</i>., not significant.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206404, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g006", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Activation_of_STAT3_which_was_negatively_regulated_by_SH3BGR_contributes_to_miR-K6-3p-induced_endothelial_cell_migration_and_angiogenesis_/3206404", "title"=>"Activation of STAT3, which was negatively regulated by SH3BGR, contributes to miR-K6-3p-induced endothelial cell migration and angiogenesis.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032786"], "description"=>"<p><b>(A)</b>. Transwell migration assay for HUVEC were treated with PBS (PBS), infected with BAC16 KSHV wide type virus (KSHV_WT) or BAC16 KSHV miR-K6 deletion mutant virus (miR-K6_Mut). The representative images were captured at 6 and 12 h post seeding (original magnification, ×100). <b>(B)</b>. Quantification of the results in (<b>A</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. (<b>C</b>). Microtubule formation assay for HUVEC treated as in (<b>A</b>). The representative images were captured at 3 and 6 h post seeding (original magnification, ×100). <b>(D)</b>. Quantification of the results in (<b>C</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(E)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in HUVEC treated as in (<b>A</b>) were determined by RT-qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(F)</b>. Western blotting analysis of expression of SH3BGR, phosphorylated STAT3, STAT3 and VEGFA in HUVEC treated as in (<b>A</b>) with the indicated antibodies. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206407, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Deletion_of_miR-K6_from_KSHV_genome_attenuates_KSHV_induction_of_endothelial_cell_migration_and_angiogenesis_/3206407", "title"=>"Deletion of miR-K6 from KSHV genome attenuates KSHV induction of endothelial cell migration and angiogenesis.", "pos_in_sequence"=>8, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032789"], "description"=>"<p><b>(A)</b>. Western blotting analysis of expression of SH3BGR, phosphorylated STAT3 and STAT3 in HUVEC infected with BAC16 KSHV wide type virus (<b>KSHV_WT</b>) or BAC16 KSHV miR-K6 deletion mutant virus (<b>miR-K6_Mut</b>) and further transduced with lentivirus-mediated a mixture of short hairpin RNAs targeting SH3BGR (<b>shSH3BGR</b>). Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(B)</b>. Transwell migration assay for HUVEC treated as in (<b>A</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05 and ** <i>P</i> < 0.01 for Student’s <i>t</i>-test. <b>(C)</b>. Microtubule formation assay for HUVEC treated as in (<b>A</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(D)</b>. Western blotting analysis of expression of phosphorylated STAT3 and STAT3 in HUVEC infected with BAC16 KSHV wide type virus (<b>KSHV_WT</b>) or BAC16 KSHV miR-K6 deletion mutant virus (<b>miR-K6_Mut</b>) and further tranfected with pCMV3-Flag-STAT3 construct (<b>STAT3</b>) or its control pCMV3-C-Flag (<b>pCMV</b>). The antibody against Flag-tag was used to detect the exogenous expression of STAT3. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(E)</b>. Transwell migration assay for HUVEC treated as in (<b>D</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05 and ** <i>P</i> < 0.01 for Student’s <i>t</i>-test. <b>(F)</b>. Microtubule formation assay for HUVEC treated as in (<b>D</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01, and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(G)</b>. Schematic representation of the mechanism by which miR-K6-3p facilitates endothelial cell migration and angiogenesis. In normal endothelial cells, SH3BGR binds STAT3 to inhibit STAT3 activation. During KSHV infection, reduction of SH3BGR as a result of miR-K6-3p targeting releases STAT3 to activate STAT3, leading to the higher expression level of matrix metalloproteinases (MMPs) and angiogenic factors, and ultimately promotes endothelial cell migration and angiogenesis.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206410, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g008", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/SH3BGR_STAT3_signaling_partially_mediates_miR-K6-induced_endothelial_cell_migration_and_angiogenesis_/3206410", "title"=>"SH3BGR/STAT3 signaling partially mediates miR-K6-induced endothelial cell migration and angiogenesis.", "pos_in_sequence"=>9, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032792"], "description"=>"<p>Cellular proteins downregulated >2.0 folds in HUVEC infected with miR-K6-3p.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206413, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Cellular_proteins_downregulated_2_0_folds_in_HUVEC_infected_with_miR-K6-3p_/3206413", "title"=>"Cellular proteins downregulated >2.0 folds in HUVEC infected with miR-K6-3p.", "pos_in_sequence"=>10, "defined_type"=>3, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032795"], "description"=>"<p>Fold changes for selected proteins identified in miR-K6-3p-transduced HUVEC using TMT quantification.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206416, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Fold_changes_for_selected_proteins_identified_in_miR-K6-3p-transduced_HUVEC_using_TMT_quantification_/3206416", "title"=>"Fold changes for selected proteins identified in miR-K6-3p-transduced HUVEC using TMT quantification.", "pos_in_sequence"=>11, "defined_type"=>3, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032738", "https://ndownloader.figshare.com/files/5032762", "https://ndownloader.figshare.com/files/5032759", "https://ndownloader.figshare.com/files/5032756", "https://ndownloader.figshare.com/files/5032753", "https://ndownloader.figshare.com/files/5032750", "https://ndownloader.figshare.com/files/5032747", "https://ndownloader.figshare.com/files/5032744", "https://ndownloader.figshare.com/files/5032741", "https://ndownloader.figshare.com/files/5032765"], "description"=>"<div><p>Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a gammaherpesvirus etiologically associated with KS, a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells. KSHV encodes 25 mature microRNAs but their roles in KSHV-induced tumor dissemination and angiogenesis remain unknown. Here, we investigated KSHV-encoded miR-K12-6-3p (miR-K6-3p) promotion of endothelial cell migration and angiogenesis, which are the underlying mechanisms of tumor dissemination and angiogenesis. We found that ectopic expression of miR-K6-3p promoted endothelial cell migration and angiogenesis. Mass spectrometry, bioinformatics and luciferase reporter analyses revealed that miR-K6-3p directly targeted sequence in the 3’ untranslated region (UTR) of SH3 domain binding glutamate-rich protein (SH3BGR). Overexpression of SH3BGR reversed miR-K6-3p induction of cell migration and angiogenesis. Mechanistically, miR-K6-3p downregulated SH3BGR, hence relieved STAT3 from SH3BGR direct binding and inhibition, which was required for miR-K6-3p maximum activation of STAT3 and induction of cell migration and angiogenesis. Finally, deletion of miR-K6 from the KSHV genome abrogated its effect on the SH3BGR/STAT3 pathway, and KSHV-induced migration and angiogenesis. Our results illustrated that, by inhibiting SH3BGR, miR-K6-3p enhances cell migration and angiogenesis by activating the STAT3 pathway, and thus contributes to the dissemination and angiogenesis of KSHV-induced malignancies.</p></div>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206386, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005605.s001", "https://dx.doi.org/10.1371/journal.ppat.1005605.s009", "https://dx.doi.org/10.1371/journal.ppat.1005605.s008", "https://dx.doi.org/10.1371/journal.ppat.1005605.s007", "https://dx.doi.org/10.1371/journal.ppat.1005605.s006", "https://dx.doi.org/10.1371/journal.ppat.1005605.s005", "https://dx.doi.org/10.1371/journal.ppat.1005605.s004", "https://dx.doi.org/10.1371/journal.ppat.1005605.s003", "https://dx.doi.org/10.1371/journal.ppat.1005605.s002", "https://dx.doi.org/10.1371/journal.ppat.1005605.s010"], "stats"=>{"downloads"=>10, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_SH3BGR_STAT3_Pathway_Regulates_Cell_Migration_and_Angiogenesis_Induced_by_a_Gammaherpesvirus_MicroRNA/3206386", "title"=>"The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032798"], "description"=>"<p>The sequences of the shRNAs.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206419, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_sequences_of_the_shRNAs_/3206419", "title"=>"The sequences of the shRNAs.", "pos_in_sequence"=>12, "defined_type"=>3, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032768"], "description"=>"<p><b>(A)</b>. Transwell migration for HUVEC transduced with 1 MOI lentivirus empty vector (<b>mpCDH</b>) or lentivirus-miR-K6-3p (<b>miR-K6-3p</b>). The representative images were captured at 6 and 12 h post seeding (original magnification, ×100). <b>(B)</b>. The quantification results of Transwell migration assay in (<b>A</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing at least four technical replicates. <b>(C)</b>. Microtubule formation assay for HUVEC transduced with lentivirus empty vector (<b>mpCDH</b>; top) or lentivirus-miR-K6-3p (<b>miR-K6-3p</b>; bottom). The representative images were captured under the light microscope (<b>Phase</b>) and fluorescent microscope (<b>RFP</b>) at 2 and 5 h post seeding (original magnification, ×100). <b>(D)</b>. The quantification results of microtubule formation assay in (<b>C</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. <b>(E)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in HUVEC treated as in (<b>A</b>) was determined by RT-qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. ** <i>P</i> < 0.01 for Student’s <i>t</i>-test versus mpCDH group. <b>(F)</b>. Western blotting analysis of the expression of VEGFA protein in HUVEC treated as in (<b>A</b>). Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(G)</b>. HUVEC treated as in (<b>A</b>) were examined for their proangiogenic effects in Matrigel plug assay in nude mice as described in the “Materials and Methods” section. Representative photographs of angiogenesis in the nude mice are shown. <b>(H)</b>. The hemoglobin level of the Matrigel plugs treated as in (<b>G</b>) was determined with hemoglobin content calculated based on the standard curve. Data represent mean ± SD, each group with five tumors (n = 5). Three independent experiments were performed and similar results were obtained. ** <i>P</i> < 0.01 for Student’s <i>t</i>-test versus mpCDH group. <b>(I)</b>. Hematoxylin and eosin staining analysis of histologic features (<b>left</b>; ×400) and immunohistochemical (IHC) staining analysis of the expression of SMA (<b>middle</b>; ×400) and VEGFA (<b>right</b>; ×400) in plugs induced by HUVEC transduced with mpCDH or miR-K6-3p. Black arrows point to neovascularization and hemorrihagic foci in H&E staining sections and the SMA in IHC staining sections, respectively. <b>(J)</b>. Quantification of results in (<b>I</b>). ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test versus mpCDH group. <b>(K)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in the Matrigel plugs treated as in <b>(G)</b> were determined by RT-qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test versus mpCDH group.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206389, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Ectopic_expression_of_miR-K6-3p_promotes_endothelial_cell_migration_and_angiogenesis_/3206389", "title"=>"Ectopic expression of miR-K6-3p promotes endothelial cell migration and angiogenesis.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032801"], "description"=>"<p>The sequences of specific primers for qPCR.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206422, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.t004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_sequences_of_specific_primers_for_qPCR_/3206422", "title"=>"The sequences of specific primers for qPCR.", "pos_in_sequence"=>13, "defined_type"=>3, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032771"], "description"=>"<p><b>(A)</b>. Luciferase activity was detected in HEK293T cells co-transfected by a mimic of miR-K6-3p (<b>miR-K6-3p</b>) or a negative control nucleotide of miRNA (<b>Neg. Ctrl.</b>) together with pGL3-Control (<b>pGL3-Control</b>), pGL3-DUSP12 3'UTR luciferase reporter (<b>DUSP12-3’UTR</b>), pGL3-SH3BGR 3’UTR luciferase reporter (<b>SH3BGR-3’UTR</b>) or pGL3-TCF3 3’UTR luciferase reporter (<b>TCF3-3’UTR</b>) for 24 h. The relative reporter activity level of pGL3-Control, DUSP12-3'UTR, SH3BGR-3’UTR or TCF3-3’UTR in the Neg. Ctrl. group was set as ‘‘1” for comparison, respectively. ** <i>P</i> < 0.01 for Student’s <i>t</i>-test versus Neg. Ctrl. group. <b>(B)</b>. The expression of SH3BGR protein in HUVEC transduced with lentivirus empty vector (<b>mpCDH</b>) or lentivirus-miR-K6-3p (<b>miR-K6-3p</b>) was detected by Western blotting. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(C)</b>. The mRNA level of SH3BGR in HUVEC transduced with lentivirus empty vector (<b>mpCDH</b>) or lentivirus-miR-K6-3p (<b>miR-K6-3p</b>) was examined by qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. * <i>P</i> < 0.05 for Student’s <i>t</i>-test versus mpCDH group. <b>(D)</b>. Western blotting analysis of the expression of SH3BGR protein in KSHV-infected HUVEC (<b>KSHV</b>) as described in the 'Materials and Methods' section or in HUVEC treated with PBS as the negative control (<b>Mock</b>). Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(E)</b>. qPCR analysis for SH3BGR mRNA in KSHV-infected HUVEC (<b>KSHV</b>) as described in the 'Materials and Methods' section or in HUVEC treated with PBS as the negative control (<b>Mock</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. *** <i>P</i> < 0.001 for Student’s <i>t</i>-test versus Mock group. <b>(F)</b>. Hematoxylin and eosin (H&E) staining of KS lesion (<b>bottom</b>) and normal skin (<b>top</b>) to show histologic features (left panel; original magnification, ×200) and immunohistochemical (IHC) staining of KSHV LANA and SH3BGR (middle and right panels, respectively; original magnification, ×200). <b>(G)</b>. Quantification of results in <b>(F)</b>. *** <i>P</i> < 0.001 for Student’s <i>t</i>-test versus Normal skin group.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206392, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/SH3BGR_expression_is_reduced_in_miR-K6-3p-expressing_HUVEC_and_KS_lesion_samples_/3206392", "title"=>"SH3BGR expression is reduced in miR-K6-3p-expressing HUVEC and KS lesion samples.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032774"], "description"=>"<p><b>(A).</b> Luciferase assay of HEK293T cells co-transfected with pGL3-SH3BGR 3′UTR reporter together with an increasing amount (10, 20, and 50 nM) of negative control nucleotide of miRNA (<b>Neg. Ctrl.</b>) or a mimic of miR-K6-3p (<b>miR-K6-3p</b>) for 24 h. <b>(B).</b> HUVEC transfected with an increasing amount (20 and 50 nM) mimic of miR-K6-3p or negative control for 48 h. The transfected cells were collected and Western blotting was performed with the indicated antibodies. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(C).</b> Schematic illustration of the putative seed sequences of miR-K6-3p complementary with SH3BGR 3’UTR and mutagenesis of binding sites in the 3’UTR of SH3BGR. <b>(D).</b> Effect of mutation of the putative binding site on the SH3BGR 3’UTR reporter. After co-transfection of SH3BGR wild type 3’UTR (<b>WT SH3BGR</b>) or the mutant SH3BGR 3’UTR construct (<b>mut SH3BGR</b>) together with a negative control nucleotide of miRNA (<b>Neg. Ctrl.</b>), a mimic of miR-K6-3p (<b>miR-K6-3p</b>) or a mutant mimic of miR-K6-3p (<b>mut miR-K6-3p</b>) for 24 h in HEK293T cells, cells were collected and assayed for luciferase activity. * <i>P</i> < 0.05 for Student’s <i>t</i>-test versus Neg. Ctrl. group. <b>(E).</b> Mutant miR-K6-3p failed to target endogenous SH3BGR in HUVEC. A miRNA negative control nucleotide (<b>Neg. Ctrl.</b>), a mimic of miR-K6-3p (<b>miR-K6-3p mimic</b>; 10 nM) or a mutant mimic of miR-K6-3p (<b>mut miR-K6-3p</b>) lacking the seed sequences were transfected into HUVEC for 48 h, respectively. The transfected cells were collected and Western blotting was performed with the indicated antibodies. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(F).</b> Transfection of miR-K6-3p mimic (20 nM) has the same inhibition level on SH3BGR expression as that of KSHV infection. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206395, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/SH3BGR_is_directly_targeted_by_miR-K6-3p_/3206395", "title"=>"SH3BGR is directly targeted by miR-K6-3p.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/5032777"], "description"=>"<p><b>(A)</b>. Transwell migration assay for HUVEC transduced with lentivirus-mediated miR-K6-3p (<b>miR-K6-3p</b>) or empty vector (<b>mpCDH</b>), which were subsequently co-transduced with lentivirus-SH3BGR (<b>SH3BGR</b>) or its control pHAGE (<b>pHAGE</b>), respectively. The representative images were captured at 6 and 12 h post seeding (original magnification, ×100). <b>(B)</b>. Quantification of results in <b>(A)</b>. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(C)</b>. Microtubule formation assay for HUVEC treated as in (<b>A</b>). The representative images were captured at 2 and 5 h post seeding (original magnification, ×100). <b>(D)</b>. Quantification of results in (<b>C</b>). The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing five technical replicates. ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <b>(E)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in HUVEC treated as in (<b>A</b>) were determined by qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <i>n</i>.<i>s</i>., not significant. <b>(F)</b>. Western blotting was performed in HUVEC treated as in (<b>A</b>) with the indicated antibodies. The antibody against Flag-tag was used to detect the exogenous expression of SH3BGR. Results shown were from a representative experiment of three independent experiments with similar results. The values of density of protein bands after normalization to housekeeping were shown. <b>(G)</b>. HUVEC treated as in (<b>A</b>) were examined for their proangiogenic effects in Matrigel plug assay in nude mice as described in the “Materials and Methods” section. Representative photographs of angiogenesis in the nude mice are shown. <b>(H)</b>. The hemoglobin level of the Matrigel plugs treated as in (<b>G</b>) was determined with hemoglobin content calculated based on the standard curve. Data represent mean ± SD, each group with five tumors (n = 5). Three independent experiments were performed and similar results were obtained. <b>(I)</b>. The mRNA expression of MMP1, MMP13, VEGFA and VEGFR2 in the Matrigel plugs treated as in (G) were determined by qPCR. The quantified results represent the mean ± SD. Three independent experiments were performed and similar results were obtained, each experiment containing four technical replicates. * <i>P</i> < 0.05, ** <i>P</i> < 0.01 and *** <i>P</i> < 0.001 for Student’s <i>t</i>-test. <i>n</i>.<i>s</i>., not significant.</p>", "links"=>[], "tags"=>["SH 3BGR", "luciferase reporter analyses", "SH 3BGR Pathway Regulates Cell Migration", "angiogenesi", "STAT 3", "SH 3BGR Overexpression", "STAT 3 pathway", "cell migration", "KSHV encodes 25", "SH 3BGR pathway", "UTR"], "article_id"=>3206398, "categories"=>["Biophysics", "Cell Biology", "Genetics", "Molecular Biology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Infectious Diseases", "Virology"], "users"=>["Wan Li", "Qin Yan", "Xiangya Ding", "Chenyou Shen", "Minmin Hu", "Ying Zhu", "Di Qin", "Hongmei Lu", "Brian J. Krueger", "Rolf Renne", "Shou-Jiang Gao", "Chun Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005605.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Overexpression_of_SH3BGR_inhibits_miR-K6-3p-induced_endothelial_cell_migration_and_angiogenesis_i_in_vitro_i_and_i_in_vivo_i_/3206398", "title"=>"Overexpression of SH3BGR inhibits miR-K6-3p-induced endothelial cell migration and angiogenesis <i>in vitro</i> and <i>in vivo</i>.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-29 03:30:01"}

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  • {"unique-ip"=>"15", "full-text"=>"10", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"6", "full-text"=>"8", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"17", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"13", "full-text"=>"14", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"17", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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