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

Ching Ju Shen, Ya-Min Cheng, Chiu Lin Wang

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)637-644
Number of pages8
JournalJournal of Drug Targeting
Volume25
Issue number7
DOIs
Publication statusPublished - 2017 Aug 9

Fingerprint

Plasmacytoma
Epithelial-Mesenchymal Transition
Uterine Cervical Neoplasms
Genes
Genetic Promoter Regions
Paclitaxel
Long Noncoding RNA
Gene Knockdown Techniques
Histones
Neoplasms
Gene Expression

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

@article{8668f955b6524c4b8633a1abeded56de,
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.",
author = "Shen, {Ching Ju} and Ya-Min Cheng and Wang, {Chiu Lin}",
year = "2017",
month = "8",
day = "9",
doi = "10.1080/1061186X.2017.1307379",
language = "English",
volume = "25",
pages = "637--644",
journal = "Journal of Drug Targeting",
issn = "1061-186X",
publisher = "Informa Healthcare",
number = "7",

}

LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells. / Shen, Ching Ju; Cheng, Ya-Min; Wang, Chiu Lin.

In: Journal of Drug Targeting, Vol. 25, No. 7, 09.08.2017, p. 637-644.

Research output: Contribution to journalArticle

TY - JOUR

T1 - LncRNA PVT1 epigenetically silences miR-195 and modulates EMT and chemoresistance in cervical cancer cells

AU - Shen, Ching Ju

AU - Cheng, Ya-Min

AU - Wang, Chiu Lin

PY - 2017/8/9

Y1 - 2017/8/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85017136968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017136968&partnerID=8YFLogxK

U2 - 10.1080/1061186X.2017.1307379

DO - 10.1080/1061186X.2017.1307379

M3 - Article

C2 - 28296507

AN - SCOPUS:85017136968

VL - 25

SP - 637

EP - 644

JO - Journal of Drug Targeting

JF - Journal of Drug Targeting

SN - 1061-186X

IS - 7

ER -