LncRNA PVT1 epigenetically stabilizes and post-transcriptionally regulates FOXM1 by acting as a microRNA sponge and thus promotes malignant behaviors of ovarian cancer cells

Ke Yi; Minmin Hou; Jialing Yuan; Lingyun Yang; Xi Zeng; Mingrong Xi; Jie Chen

LncRNA PVT1 epigenetically stabilizes and post-transcriptionally regulates FOXM1 by acting as a microRNA sponge and thus promotes malignant behaviors of ovarian cancer cells

Am J Transl Res. 2020 Jun 15;12(6):2860-2874. eCollection 2020.

Authors

Ke Yi^{1

2}, Minmin Hou^{1

2}, Jialing Yuan^{1

2}, Lingyun Yang^{1

2}, Xi Zeng^{1

2}, Mingrong Xi^{1

2}, Jie Chen^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University No. 20, Section 3, RenminNanlu Road, Chengdu 610041, Sichuan, China.
² The Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education Chengdu 610041, Sichuan, China.

PMID: 32655815
PMCID: PMC7344089

Abstract

Accumulating evidence demonstrates that long noncoding RNAs (lncRNAs) may be involved in the regulation of cancer biology. PVT1, which is overexpressed in tumor samples, acts as an oncogenic promoter in several kinds of cancers, including ovarian cancer. However, the mechanisms of its regulation of malignant behaviors in ovarian cancer remain largely unknown. In this study, the expression of PVT1 in several ovarian cancer cell lines was analyzed by qRT-PCR. The effect of PVT1 on malignant behaviors, including cell proliferation, migration and invasion, was analyzed. The posttranscriptional regulation of FOXM1 by PVT1 was analyzed by western blotting. The results illustrated that PVT1 acted as a sponge and bound miR-370 on two binding sites. The expression of PVT1 positively regulated malignant behaviors in ovarian cancer cells, including cell proliferation, migration and invasion, which could be reversed by the introduction of miR-370 mimics. Sponged miR-370 failed to posttranscriptionally regulate FOXM1, which resulted in the promotion of malignant behavior. PVT1 was also found to bind to FOXM1 directly and stabilize the FOXM1 protein. The promoting effect of PVT1 on malignant behaviors and chemoresistance to cisplatin could be reversed by knockdown of FOXM1 and introduction of miR-370 mimics. Together, these results suggest that lncRNA PVT1 promotes malignant behavior and induces chemoresistance in ovarian cancer by epigenetic and posttranscriptional regulation of FOXM1.

Keywords: FOXM1; Long non-coding RNAs (lncRNAs); malignancy; microRNA sponge; ovarian cancer.