Feedback Regulations of miR-21 and MAPKs via Pdcd4 and Spry1 Are Involved in Arsenite-Induced Cell Malignant Transformation
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{"title"=>"Feedback Regulations of miR-21 and MAPKs via Pdcd4 and Spry1 Are Involved in Arsenite-Induced Cell Malignant Transformation", "type"=>"journal", "authors"=>[{"first_name"=>"Lu", "last_name"=>"Shen", "scopus_author_id"=>"57199824167"}, {"first_name"=>"Min", "last_name"=>"Ling", "scopus_author_id"=>"36161823500"}, {"first_name"=>"Yuan", "last_name"=>"Li", "scopus_author_id"=>"55904677600"}, {"first_name"=>"Yuan", "last_name"=>"Xu", "scopus_author_id"=>"55140117400"}, {"first_name"=>"Yun", "last_name"=>"Zhou", "scopus_author_id"=>"56184784200"}, {"first_name"=>"Jing", "last_name"=>"Ye", "scopus_author_id"=>"55613250500"}, {"first_name"=>"Ying", "last_name"=>"Pang", "scopus_author_id"=>"54080179700"}, {"first_name"=>"Yue", "last_name"=>"Zhao", "scopus_author_id"=>"56584972100"}, {"first_name"=>"Rongrong", "last_name"=>"Jiang", "scopus_author_id"=>"55141917600"}, {"first_name"=>"Jianping", "last_name"=>"Zhang", "scopus_author_id"=>"7601343102"}, {"first_name"=>"Qizhan", "last_name"=>"Liu", "scopus_author_id"=>"8374316800"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23469214", "sgr"=>"84874572210", "doi"=>"10.1371/journal.pone.0057652", "scopus"=>"2-s2.0-84874572210", "pui"=>"368451375", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"28a867d1-22fa-3d33-83c5-7e4d1378755c", "abstract"=>"OBJECTIVE: To establish the functions of miR-21 and the roles of two feedback regulation loops, miR-21-Spry1-ERK/NF-κB and miR-21-Pdcd4-JNK/c-Jun, in arsenite-transformed human embryo lung fibroblast (HELF) cells.\\n\\nMETHODS: For arsenite-transformed HELF cells, apoptosis, clonogenicity, and capacity for migration were determined by Hoechst staining, assessment of their capacity for anchorage-independent growth, and wound-healing, respectively, after blockage, with inhibitors or with siRNAs, of signal pathways for JNK/c-Jun or ERK/NF-κB. Decreases of miR-21 levels were determined with anti-miR-21, and the up-regulation of Pdcd4 and Spry1 was assessed in transfected cells; these cells were molecularly characterized by RT-PCR, qRT-PCR, Western blots, and immunofluorescence assays.\\n\\nRESULTS: MiR-21 was highly expressed in arsenite-transformed HELF cells and normal HELF cells acutely treated with arsenite, an effect that was concomitant with activation of JNK/c-Jun and ERK/NF-κB and down-regulation of Pdcd4 and Spry1 protein levels. However, there were no significant changes in mRNA levels for Pdcd4 and Spry1, which suggested that miR-21 regulates the expressions of Pdcd4 and Spry1 through translational repression. In arsenite-transformed HELF cells, blockages of JNK/c-Jun or ERK/NF-κB with inhibitors or with siRNAs prevented the increases of miR-21and the decreases of the protein levels but not the mRNA levels of Pdcd4 and Spry1. Down-regulation of miR-21 and up-regulations of Pdcd44 or Spry1 blocked the arsenite-induced activations of JNK/c-Jun or ERK/NF-κB, indicating that knockdown of miR-21 inhibits feedback of ERK activation and JNK activation via increases of Pdcd4 and Spry1 protein levels, respectively. Moreover, in arsenite-transformed HELF cells, inhibition of miR-21 promoted cell apoptosis, inhibited clonogenicity, and reduced migration.\\n\\nCONCLUSION: The results indicate that miR-21 is both a target and a regulator of ERK/NF-κB and JNK/c-Jun and the feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1, respectively, are involved in arsenite-induced malignant transformation of HELF cells.", "link"=>"http://www.mendeley.com/research/feedback-regulations-mir21-mapks-via-pdcd4-spry1-involved-arseniteinduced-cell-malignant-transformat", "reader_count"=>15, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>2, "Unspecified"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/976177"], "description"=>"<p>Abbreviations: HELF-C, normal HELF cells; HELF-30C, passage-control HELF cells; HELF-30T, arsenite-transformed HELF cells. Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. HELF cells were exposed to 0.0 or 1.0 µM arsenite for 30 passages. (A, B) Western blot analyses and (C) relative protein levels (means ± SD, n = 3) of p-ERK, p-JNK, and p-p38 (representative of MAPKs signal pathways); p- NF-κB 65 and p-c-Jun levels (representative transcription factors); and p-Akt level (representative of the PI-3Ks signal pathway). **<i>P</i><0.01 different from HELF-30C cells.</p>", "links"=>[], "tags"=>["akt", "induced", "arsenite-transformed", "helf"], "article_id"=>643759, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Activations_of_ERK_NF_954_B_JNK_c_Jun_and_Akt_are_induced_in_arsenite_transformed_HELF_cells_/643759", "title"=>"Activations of ERK/NF-κB, JNK/c-Jun, and Akt are induced in arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:21:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/976181"], "description"=>"<p>Abbreviations: HELF-C, normal HELF cells; HELF-30C, passage-control HELF cells; HELF-30T, arsenite-transformed HELF cells. Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. HELF cells were exposed to 0.0 or 1.0 µM arsenite for 30 passages. (A) The levels of miR-21 were determined by qRT-PCR assays (means ± SD, n = 3). **<i>P</i><0.01 different from HELF-30C cells. (B) The protein levels (upper) and mRNA levels (lower) of Pdcd4 and Spry1 (target proteins of miR-21) were analyzed by Western blots and RT-PCR, respectively. (C) The relative protein levels of Pdcd4 and Spry1 (means ± SD, n = 3). **<i>P</i><0.01 different from HELF-30C cells.</p>", "links"=>[], "tags"=>["mir-21", "pdcd4", "spry1", "arsenite-transformed", "helf"], "article_id"=>643763, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_level_of_miR_21_is_up_regulated_and_the_protein_levels_of_Pdcd4_and_Spry1_are_decreased_in_arsenite_transformed_HELF_cells_/643763", "title"=>"The level of miR-21 is up-regulated, and the protein levels of Pdcd4 and Spry1 are decreased in arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/976184"], "description"=>"<p>Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. Arsenite-transformed HELF cells were treated with 10 µM of LY294002 (an inhibitor of PI-3K), SP600125 (an inhibitor of JNK), or U0126 (an inhibitor of ERK) for 24 h. (A) Western blots and (B) relative protein levels (means ± SD, n = 3) of p-Akt, p-ERK, and p-JNK. (C) qRT-PCR analysis of miR-21 expression (means ± SD, n = 3). **<i>P</i><0.01 difference from control group. (D) Western blots (upper) and RT-PCR (below) analyses for protein and mRNA levels and (E) relative protein levels (means ± SD, n = 3) of Pdcd4, Spry1, cleaved-caspase-3, and caspase-3. **<i>P</i><0.01 difference from control group.</p>", "links"=>[], "tags"=>["jnk", "regulations", "mir-21", "pdcd4", "spry1", "apoptosis", "arsenite-transformed", "helf"], "article_id"=>643765, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ERK_and_JNK_are_involved_in_the_regulations_of_miR_21_to_protein_levels_of_Pdcd4_and_Spry1_and_to_cell_apoptosis_in_arsenite_transformed_HELF_cells_/643765", "title"=>"ERK and JNK are involved in the regulations of miR-21 to protein levels of Pdcd4 and Spry1 and to cell apoptosis in arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:22:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/976187"], "description"=>"<p>Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. Arsenite-transformed HELF cells were transfected with 50 nM of control siRNA, NF-κB p65 siRNA, or c-Jun siRNA for 24 h. (A) Western blots and (B) relative protein levels (means ± SD, n = 3) of NF-κB p65 and c-Jun. (C) qRT-PCR analysis of miR-21 expression (means ± SD, n = 3). **<i>P</i><0.01 difference from Con siRNA group. (D) Western blots (upper) and RT-PCR (below) analyses for protein and mRNA levels and (E) relative protein levels (means ± SD, n = 3) of Pdcd4, Spry1, cleaved-caspase-3, and caspase-3, **<i>P</i><0.01 difference from the control (Con) siRNA group.</p>", "links"=>[], "tags"=>["c-jun", "regulations", "mir-21", "pdcd4", "spry1", "apoptosis", "arsenite-transformed", "helf"], "article_id"=>643768, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NF_954_B_and_c_Jun_are_involved_in_the_regulations_of_miR_21_to_protein_levels_of_Pdcd4_and_Spry1_and_to_cell_apoptosis_in_arsenite_transformed_HELF_cells_/643768", "title"=>"NF-κB and c-Jun are involved in the regulations of miR-21 to protein levels of Pdcd4 and Spry1 and to cell apoptosis in arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:22:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/976190"], "description"=>"<p>Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. Arsenite-transformed HELF cells were transfected with 150 nM of anti-miR-nc or anti-miR-21 for 24 h. (A) Western blots (upper) and RT-PCR (below) analyses for protein and mRNA levels of Pdcd4 and Spry1, respectively. (B) Relative protein levels of Pdcd4 and Spry1 (means ± SD, n = 3). **<i>P</i><0.01 different from NC group. Normal HELF cells were transfected with 100 nM of miR-nc-mimic or miR-21-mimic for 24 h. (C) Western blots (upper) and RT-PCR (below) analyses for protein and mRNA levels of Pdcd4 and Spry1, respectively. (D) Relative protein levels of Pdcd4 and Spry1 (means ± SD, n = 3). **<i>P</i><0.01 different from NC group.</p>", "links"=>[], "tags"=>["spry1", "proteins"], "article_id"=>643770, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pdcd4_and_Spry1_are_target_proteins_of_miR_21_/643770", "title"=>"Pdcd4 and Spry1 are target proteins of miR-21.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:23:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/976193"], "description"=>"<p>Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. Arsenite-transformed HELF cells were transfected with 150 nM of anti-miR-nc or anti-miR-21 for 24 h. (A) Western blots and (B) relative protein levels (means ± SD, n = 3) of p-ERK, p-JNK, Spry1, and Pdcd4. **<i>P</i><0.01 different from NC group. Arsenite-transformed HELF cells were transfected with pIRES, pIRES-Pdcd4, or pIRES-Spry1 for 24 h. (C) Western blots and (D) relative protein levels (means ± SD, n = 3) of p-JNK, p-c-Jun, and Pdcd4. (E) qRT-PCR analysis of miR-21 expression (means ± SD, n = 3). **<i>P</i><0.01 different from control group. (F) Western blots and (G) relative protein levels (means ± SD, n = 3) of p-ERK, p-NF-κB p65, and Spry1. (H) qRT-PCR analysis of miR-21 expression (means ± SD, n = 3). **<i>P</i><0.01 different from control group.</p>", "links"=>[], "tags"=>["activations", "erk", "jnk", "feedback-regulated", "mir-21", "spry1", "arsenite-", "transformed", "helf"], "article_id"=>643772, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_activations_of_ERK_and_JNK_are_feedback_regulated_by_miR_21_via_Spry1_and_Pdcd4_respectively_in_arsenite_transformed_HELF_cells_/643772", "title"=>"The activations of ERK and JNK are feedback-regulated by miR-21 via Spry1 and Pdcd4, respectively, in arsenite- transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:23:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/976197"], "description"=>"<p>Densities of bands were quantified by Eagle Eye II software. GAPDH levels, measured in parallel, served as controls. Arsenite-transformed HELF cells were transfected with 150 nM of anti-miR-nc or anti-miR-21 for 24 h. (A) Western blots and (B) relative protein levels of cleaved caspase-3 and caspase-3 (means ± SD, n = 3). **<i>P</i><0.01 different from NC group. (C) The rate of cell apoptosis was analyzed by the Hoechst 33258 assay (means ± SD, n = 3). **<i>P</i><0.01 different from NC group.</p>", "links"=>[], "tags"=>["mir-21", "apoptosis", "arsenite-transformed", "helf"], "article_id"=>643776, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_miR_21_increases_cell_apoptosis_of_arsenite_transformed_HELF_cells_/643776", "title"=>"Inhibition of miR-21 increases cell apoptosis of arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:24:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/976201"], "description"=>"<p>After arsenite-transformed HELF cells were transfected with or without anti-miR-21 (150 nM) for 24 h, the neoplastic capacity and motility of cells were determined by anchorage-independent growth and scratch wound healing assays, respectively, bars = 100 µm. (A) Cell colony and (B) their numbers (means ± SD, n = 3) in soft agar. **<i>P</i><0.01 difference from NC group. (C) Movement of cells into the wound and (D) the percentages of open space areas covered (means ± SD, n = 3). **<i>P</i><0.01 difference from NC group.</p>", "links"=>[], "tags"=>["mir-21", "decreases", "neoplastic", "motility", "arsenite-transformed", "helf"], "article_id"=>643780, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_miR_21_decreases_the_neoplastic_capacity_and_motility_of_arsenite_transformed_HELF_cells_/643780", "title"=>"Inhibition of miR-21 decreases the neoplastic capacity and motility of arsenite-transformed HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/976204"], "description"=>"<p>In arsenite-transformed HELF cells, miR-21 levels are up-regulated by the activations of ERK/NF-κB and JNK/c-Jun. miR-21 inhibits the target proteins, Pdcd4 and Spry1, which form two feedback regulation loops, miR-21-Spry1-ERK/NF-κB and miR-21-Pdcd4-JNK/c-Jun.</p>", "links"=>[], "tags"=>["regulations", "mir-21", "mapks", "pdcd4", "spry1", "arsenite-induced", "malignant", "helf"], "article_id"=>643783, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Feedback_regulations_of_miR_21_and_MAPKs_via_Pdcd4_and_Spry1_in_arsenite_induced_malignant_transformation_of_HELF_cells_/643783", "title"=>"Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 in arsenite-induced malignant transformation of HELF cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-02 05:24:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/976207", "https://ndownloader.figshare.com/files/976208"], "description"=>"<div><p>Objective</p><p>To establish the functions of miR-21 and the roles of two feedback regulation loops, miR-21-Spry1-ERK/NF-κB and miR-21-Pdcd4-JNK/c-Jun, in arsenite-transformed human embryo lung fibroblast (HELF) cells.</p> <p>Methods</p><p>For arsenite-transformed HELF cells, apoptosis, clonogenicity, and capacity for migration were determined by Hoechst staining, assessment of their capacity for anchorage-independent growth, and wound-healing, respectively, after blockage, with inhibitors or with siRNAs, of signal pathways for JNK/c-Jun or ERK/NF-κB. Decreases of miR-21 levels were determined with anti-miR-21, and the up-regulation of Pdcd4 and Spry1 was assessed in transfected cells; these cells were molecularly characterized by RT-PCR, qRT-PCR, Western blots, and immunofluorescence assays.</p> <p>Results</p><p>MiR-21 was highly expressed in arsenite-transformed HELF cells and normal HELF cells acutely treated with arsenite, an effect that was concomitant with activation of JNK/c-Jun and ERK/NF-κB and down-regulation of Pdcd4 and Spry1 protein levels. However, there were no significant changes in mRNA levels for Pdcd4 and Spry1, which suggested that miR-21 regulates the expressions of Pdcd4 and Spry1 through translational repression. In arsenite-transformed HELF cells, blockages of JNK/c-Jun or ERK/NF-κB with inhibitors or with siRNAs prevented the increases of miR-21and the decreases of the protein levels but not the mRNA levels of Pdcd4 and Spry1. Down-regulation of miR-21 and up-regulations of Pdcd44 or Spry1 blocked the arsenite-induced activations of JNK/c-Jun or ERK/NF-κB, indicating that knockdown of miR-21 inhibits feedback of ERK activation and JNK activation via increases of Pdcd4 and Spry1 protein levels, respectively. Moreover, in arsenite-transformed HELF cells, inhibition of miR-21 promoted cell apoptosis, inhibited clonogenicity, and reduced migration.</p> <p>Conclusion</p><p>The results indicate that miR-21 is both a target and a regulator of ERK/NF-κB and JNK/c-Jun and the feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1, respectively, are involved in arsenite-induced malignant transformation of HELF cells.</p> </div>", "links"=>[], "tags"=>["regulations", "mir-21", "mapks", "pdcd4", "spry1", "arsenite-induced", "malignant", "transformation"], "article_id"=>643786, "categories"=>["Cancer", "Molecular Biology", "Chemistry", "Genetics"], "users"=>["Lu Shen", "Min Ling", "Yuan Li", "Yuan Xu", "Yun Zhou", "Jing Ye", "Ying Pang", "Yue Zhao", "Rongrong Jiang", "Jianping Zhang", "Qizhan Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0057652.s001", "https://dx.doi.org/10.1371/journal.pone.0057652.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Feedback_Regulations_of_miR_21_and_MAPKs_via_Pdcd4_and_Spry1_Are_Involved_in_Arsenite_Induced_Cell_Malignant_Transformation__/643786", "title"=>"Feedback Regulations of miR-21 and MAPKs via Pdcd4 and Spry1 Are Involved in Arsenite-Induced Cell Malignant Transformation", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-02 05:25:02"}

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Relative Metric

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