title: NF-κB1, c-Rel, and ELK1 inhibit miR-134 expression leading to TAB1 upregulation in paclitaxel-resistant human ovarian cancer.
abstract: The mechanism by which the transcription factors inhibit the miRNA expression in ovarian cancer chemoresistance is unclear. The present study investigated the mechanism underlying the transcriptional repression of miR-134 in chemoresistant serous epithelial ovarian cancer. The results demonstrate that NF-κB1, c-Rel, and ELK1 are involved as transcription factors in repressing miR-134 expression in paclitaxel-resistant ovarian cancer cells. Knockdown of these transcription factors led to increased miR-134 expression, resulting in increased apoptosis and inhibition of proliferation in SKOV3-TR30 cells. NF-κB1, c-Rel, and ELK1 mRNA expression was upregulated in chemoresistant specimens and negatively correlated with miR-134 expression. Kaplan-Meier analysis revealed that high nuclear expressions of NF-κB1, c-Rel, ELK1 were significantly associated with short survival in serous epithelial ovarian cancer patients. Finally, TAB1 was identified as a functional target of miR-134, and the expression of TAB1 was increased by the transcription factors of NF-κB1, c-Rel, and ELK1 via miR-134. Taken together, these results provide an insight into the mechanism of repressed miR-134 expression in chemoresistance of serous epithelial ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.|Department of Obstetrics and Gynecology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710033, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shuang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D020569:Proto-Oncogene Proteins c-rel / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C494112:ELK1 protein, human; C569273:MIRN134 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; C068059:REL protein, human; C486300:TAB1 protein, human; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D017239:Paclitaxel
keywords: miR-134; miRNA gene regulation; ovarian cancer; paclitaxel resistance; transcription factor