LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells

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 H...

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Published inJournal of drug targeting Vol. 25; no. 7; pp. 637 - 644
Main Authors Shen, Ching-Ju, Cheng, Ya-Min, Wang, Chiu-Lin
Format Journal Article
LanguageEnglish
Published England Taylor & Francis 09.08.2017
Subjects
Cell Line, Tumor
Drug Resistance, Neoplasm
Epigenesis, Genetic
Epithelial-Mesenchymal Transition - drug effects
Female
Gene Silencing
Humans
MicroRNAs - genetics
Paclitaxel - pharmacology
Promoter Regions, Genetic
PVT1; miR-195; EMT; chemoresistance; cervical cancer
RNA, Long Noncoding - genetics
RNA, Long Noncoding - physiology
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
PVT1; miR-195; EMT; chemoresistance; cervical cancer
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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.
AbstractList 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.
Author Cheng, Ya-Min
Shen, Ching-Ju
Wang, Chiu-Lin
Author_xml – sequence: 1
  givenname: Ching-Ju
  surname: Shen
  fullname: Shen, Ching-Ju
  organization: Department of Gynecology and Obstetrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University
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  givenname: Ya-Min
  surname: Cheng
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  fullname: Wang, Chiu-Lin
  organization: Department of Obstetrics and Gynecology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University
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Snippet The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the...
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SubjectTerms Cell Line, Tumor
Drug Resistance, Neoplasm
Epigenesis, Genetic
Epithelial-Mesenchymal Transition - drug effects
Female
Gene Silencing
Humans
MicroRNAs - genetics
Paclitaxel - pharmacology
Promoter Regions, Genetic
PVT1; miR-195; EMT; chemoresistance; cervical cancer
RNA, Long Noncoding - genetics
RNA, Long Noncoding - physiology
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - pathology
Title LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells
URI https://www.tandfonline.com/doi/abs/10.1080/1061186X.2017.1307379
https://www.ncbi.nlm.nih.gov/pubmed/28296507
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Volume 25
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