title: LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells.
abstract: The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region. In addition, PVT1 could competitively bind with miR-195. MiR-195 overexpression suppressed PVT1 expression in the cancer cells. Both PVT1 and miR-195 could inhibit paclitaxel (PTX) induced epithelial-to-mesenchymal transition (EMT) and also sensitize CaSki cells to PTX. Based on these findings, we infer that PVT1 could decrease miR-195 expression via enhancing histone H3K27me3 in the miR-195 promoter region and also via direct sponging of miR-195. In addition, the PVT1/miR-195 axis can modulate responses of the cancer cells to PTX via regulating EMT.
authors.affiliation: a Department of Gynecology and Obstetrics , Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Ching-Ju
authors.initials: CJ
authors.lastname: Shen
authors.affiliation: b Department of Obstetrics and Gynecology , Institute of Clinical Medicine, College of Medicine, National Cheng Kung University , Tainan , Taiwan.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Cheng
authors.affiliation: c Department of Obstetrics and Gynecology , Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University , Kaohsiung , Taiwan.
authors.forename: Chiu-Lin
authors.initials: CL
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*
chemical_list: C552722:MIRN195 microRNA, human; D035683:MicroRNAs; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; D017239:Paclitaxel
keywords: PVT1; miR-195; EMT; chemoresistance; cervical cancer