Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR-200b.
Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain-of-function and loss-of-function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR-200b promoter, increases histone H3K27 trimethylation level on the miR-200b promoter, and inhibits miR-200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR-200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer.
Department of Maternity, Yantaishan Hospital, Yantai, Shandong Province, China.
Shaorong
S
Zhang
Department of Maternity, Yantaishan Hospital, Yantai, Shandong Province, China.
Guanli
G
Zhang
Department of Maternity, Yantaishan Hospital, Yantai, Shandong Province, China.
Jingying
J
Liu
D000328:Adult; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000503:physiopathology*
D006657:Histones; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
Long noncoding RNA; cervical cancer; epigenetics; microRNA; progression