MicroRNA-196b Regulates the Homeobox B7-Vascular Endothelial Growth Factor Axis in Cervical Cancer
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{"title"=>"MicroRNA-196b Regulates the Homeobox B7-Vascular Endothelial Growth Factor Axis in Cervical Cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Christine", "last_name"=>"How", "scopus_author_id"=>"54408744400"}, {"first_name"=>"Angela B.Y.", "last_name"=>"Hui", "scopus_author_id"=>"36753047700"}, {"first_name"=>"Nehad M.", "last_name"=>"Alajez", "scopus_author_id"=>"8592996300"}, {"first_name"=>"Wei", "last_name"=>"Shi", "scopus_author_id"=>"56493703100"}, {"first_name"=>"Paul C.", "last_name"=>"Boutros", "scopus_author_id"=>"6602545313"}, {"first_name"=>"Blaise A.", "last_name"=>"Clarke", "scopus_author_id"=>"7202373058"}, {"first_name"=>"Rui", "last_name"=>"Yan", "scopus_author_id"=>"55785402100"}, {"first_name"=>"Melania", "last_name"=>"Pintilie", "scopus_author_id"=>"7004529518"}, {"first_name"=>"Anthony", "last_name"=>"Fyles", "scopus_author_id"=>"7005542664"}, {"first_name"=>"David W.", "last_name"=>"Hedley", "scopus_author_id"=>"7005745610"}, {"first_name"=>"Richard P.", "last_name"=>"Hill", "scopus_author_id"=>"7404751901"}, {"first_name"=>"Michael", "last_name"=>"Milosevic", "scopus_author_id"=>"8109671400"}, {"first_name"=>"Fei Fei", "last_name"=>"Liu", "scopus_author_id"=>"36067802500"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84879828011", "pui"=>"369260741", "pmid"=>"23861821", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0067846", "sgr"=>"84879828011"}, "id"=>"20594c3d-8ddf-3450-8324-1b0c1ac6b6b6", "abstract"=>"The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.", "link"=>"http://www.mendeley.com/research/microrna196b-regulates-homeobox-b7vascular-endothelial-growth-factor-axis-cervical-cancer", "reader_count"=>17, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>5, "Other"=>3, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>6, "Materials Science"=>1, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>5, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}}, "reader_count_by_country"=>{"India"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1111911"], "description"=>"<p>ME-180 and SiHa cells were transfected with siHOXB7, siVEGF or siNEG (30 nmol/L): <b>A)</b> Relative cell viability assessed using the Trypan blue assay at 48 and 72 hours post-transfection with siHOXB7 (left) or siVEGF (right); <b>B)</b> Cells were harvested at 48 hours post-transfection, then counted and re-seeded at low density in 6-well plates; after 10 days of incubation, cells were fixed and stained and colonies (>50 cells) were counted. Histograms depict the relative number of surviving colonies post-transfection with siHOXB7 (left), and siVEGF (right). <b>C)</b> Representative images (left) and histograms (right) depict migratory ability (top), and invasiveness (bottom) after transfection. All data represented the mean ± SEM from 3 independent experiments. siNEG, All Stars Negative Control; *<i>P</i><0.05.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "sihoxb7"], "article_id"=>740091, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downstream_effects_of_siHOXB7_and_siVEGF_/740091", "title"=>"Downstream effects of siHOXB7 and siVEGF.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111923", "https://ndownloader.figshare.com/files/1111926", "https://ndownloader.figshare.com/files/1111927", "https://ndownloader.figshare.com/files/1111929", "https://ndownloader.figshare.com/files/1111930", "https://ndownloader.figshare.com/files/1111932", "https://ndownloader.figshare.com/files/1111934"], "description"=>"<div><p>The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a <i>bona fide</i> target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion <i>in vitro</i>, as well as reduced tumor angiogenesis and tumor cell proliferation <i>in vivo</i>. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.</p></div>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "regulates", "homeobox", "b7-vascular", "endothelial", "axis", "cervical"], "article_id"=>740102, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0067846.s001", "https://dx.doi.org/10.1371/journal.pone.0067846.s002", "https://dx.doi.org/10.1371/journal.pone.0067846.s003", "https://dx.doi.org/10.1371/journal.pone.0067846.s004", "https://dx.doi.org/10.1371/journal.pone.0067846.s005", "https://dx.doi.org/10.1371/journal.pone.0067846.s006", "https://dx.doi.org/10.1371/journal.pone.0067846.s007"], "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MicroRNA_196b_Regulates_the_Homeobox_B7_Vascular_Endothelial_Growth_Factor_Axis_in_Cervical_Cancer_/740102", "title"=>"MicroRNA-196b Regulates the Homeobox B7-Vascular Endothelial Growth Factor Axis in Cervical Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111900"], "description"=>"<p><b>A)</b> Relative viability of ME-180 and SiHa cells were assessed at 48 and 72 hours post-transfection with pre-miR-196b (30 nmol/L), compared to Negative Control pre-miR (30 nmol/L), using the Trypan Blue assay. <b>B)</b> Clonogenicity of ME-180 and SiHa cells were assessed by transfection with 30 nmol/L of pre-miR 196b or Negative Control pre-miR. At 48 hours post-transfection, cells were harvested then counted and re-seeded at low density in 6-well plates. After 10 days of incubation, cells were fixed and stained and the number of colonies (>50 cells) were counted. <b>C)</b> Relative proliferation of ME-180 and SiHa cells were examined at 24, 48, and 72 hours post-transfection with pre-miR-196b (30 nmol/L), compared to Negative Control pre-miR (30 nmol/L), using the MTS assay. <b>D)</b> Representative images (left) and histograms (right) depicting migratory ability (top) and invasiveness (bottom) of ME-180 cells that were transfected with 30 nmol/L of pre-miR 196b or Negative Control pre-miR, harvested at 24 hours post-transfection, then counted and re-seeded in the invasion chambers. Cell migration (top), and invasion (bottom), assessed at 48 hours after seeding in transwell chambers. All data represent the mean ± SEM from 3 independent experiments. NC, pre-miR Negative Control; *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "vitro", "mir-196b"], "article_id"=>740081, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.g002", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_e_ffects_of_miR_196b_over_expression_/740081", "title"=>"<i>In vitro e</i>ffects of miR-196b over-expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111913"], "description"=>"<p>Clinical parameters of 79 cervical cancer patients.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "79", "cervical", "cancer"], "article_id"=>740093, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_parameters_of_79_cervical_cancer_patients_/740093", "title"=>"Clinical parameters of 79 cervical cancer patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111895"], "description"=>"<p><b>A)</b> miR-196b expression levels were measured using qRT-PCR in 79 primary cervical cancer samples, compared to 11 normal cervix epithelial tissue controls. <b>B)</b> Kaplan-Meier analysis of DFS in patients with cervical cancer. Red, patients with higher than median miR-196b expression level (n = 39); blue, patients with lower than median miR-196b expression (n = 39); one patient was removed from survival analysis due to missing survival information. <b>C)</b> Basal levels of miR-196b in three cervical cancer cell lines (SiHa, ME-180, and HT-3), as compared to normal cervix epithelial tissues, assayed by qRT-PCR. **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "down-regulation", "cervical"], "article_id"=>740078, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_196b_down_regulation_in_cervical_cancer_/740078", "title"=>"miR-196b down-regulation in cervical cancer.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111908"], "description"=>"<p><b>A)</b> Relative VEGF expression at the mRNA level after transfection of ME-180 or SiHa cells with siHOXB7 or siNEG (30 nmol/L), as determined by qRT-PCR. Expression levels were normalized to GAPDH expression. <b>B)</b> Relative levels of secreted VEGF protein after transfection of ME-180 or SiHa cells with siHOXB7 or siNEG (30 nmol/L), as determined by ELISA. All data represented the mean ± SEM from 3 independent experiments. siNEG, All Stars Negative Control; *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "vegf", "hoxb7", "transcription"], "article_id"=>740088, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_VEGF_as_a_target_of_the_HOXB7_transcription_factor_/740088", "title"=>"Identification of VEGF as a target of the HOXB7 transcription factor.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:42:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1111906"], "description"=>"<p><b>A)</b> Relative luciferase activity of ME-180 or SiHa cells at 24 hours after co-transfection with pMIR-REPORT, pMIR-HOXB7 or pMIR-HOXB7-mut vectors and pre-miR-196b or NC (30 nmol/L). <b>B)</b> Relative HOXB7 mRNA expression levels in ME-180 or SiHa cells after transfection (48, and 72 hrs) with pre-miR-196b or NC (30 nmol/L), as measured by qRT-PCR. Expression levels were normalized to GAPDH expression. <b>C)</b> Representative Western blot image (top), and relative quantification of HOXB7 protein levels (bottom) after transfection (48, and 72 hrs) with pre-miR-196b or NC (30 nmol/L). All data represented the mean ± SEM from 3 independent experiments. OD, optical density; NC, pre-miR Negative Control; *<i>P</i><0.05; **<i>P</i><0.01.</p>", "links"=>[], "tags"=>["genetics", "epigenetics", "RNA interference", "gene expression", "Molecular cell biology", "Nucleic acids", "rna", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Cervical cancer", "Basic cancer research", "hoxb7", "mrna"], "article_id"=>740086, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Christine How", "Angela B. Y. Hui", "Nehad M. Alajez", "Wei Shi", "Paul C. Boutros", "Blaise A. Clarke", "Rui Yan", "Melania Pintilie", "Anthony Fyles", "David W. Hedley", "Richard P. Hill", "Michael Milosevic", "Fei-Fei Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0067846.g003", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_HOXB7_as_an_mRNA_target_of_miR_196b_/740086", "title"=>"Identification of HOXB7 as an mRNA target of miR-196b.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-07-04 02:42:53"}

PMC Usage Stats | Further Information

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Relative Metric

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