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Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR‐200b

2016; Wiley; Volume: 124; Issue: 8 Linguagem: Inglês

10.1111/apm.12555

1600-0463

Shaorong Zhang, Guanli Zhang, Jingying Liu,

RNA modifications and cancer

Long noncoding RNA PVT 1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT 1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT 1 in cervical cancer. Our results revealed that PVT 1 is upregulated in cervical cancer tissues. Enhanced expression of PVT 1 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 PVT 1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT 1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT 1 binds to EZH 2, recruits EZH 2 to the miR‐200b promoter, increases histone H3K27 trimethylation level on the miR‐200b promoter, and inhibits miR‐200b expression. Furthermore, the effects of PVT 1 on cervical cell proliferation and migration depend upon silencing of miR‐200b. Taken together, our findings confirmed that PVT 1 functions as an oncogene in cervical cancer and indicated that PVT 1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer.