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.

Zhang S ，Zhang G ，Liu J 《-》

Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429.

Sui CJ ，Zhou YM ，Shen WF ，Dai BH ，Lu JJ ，Zhang MF ，Yang JM ... -  《-》

Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma.

Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.

Chen X ，Liu S ，Zhao X ，Ma X ，Gao G ，Yu L ，Yan D ，Dong H ，Sun W ... -  《-》

Effect of long non-coding RNA PVT1 on cell proliferation and migration in melanoma.

Chen L ，Ma D ，Li Y ，Li X ，Zhao L ，Zhang J ，Song Y ... -  《-》

DNMT1 and EZH2 mediated methylation silences the microRNA-200b/a/429 gene and promotes tumor progression.

Aberrant expression of the microRNA-200 (miR-200) family has been linked to the occurrence and development of various types of malignant tumors, including hepatocellular carcinoma (HCC), colon cancer and breast cancer. However, little is known about the precise mechanism by which miR-200 expression is downregulated. The intricate relationship between DNA methylation and histone modifications has become a subject of increasing interest. The expression of miR-200 family members is modified by similar or complementary epigenetic mechanisms in MGC-803 and BGC-823 gastric cancer cells and U87 MG glioma cells. Chromatin immunoprecipitation assays revealed that DNA methyltransferase 1 (DNMT1) bound to miR-200b/a/429 promoter regions, indicating an interaction between DNMT1 and the miR-200b/a/429 promoter. Furthermore, Co-Immunoprecipitation (Co-IP) detection showed that DNMT1, together with the PcG protein Enhancer of Zeste homolog 2 (EZH2), a histone methyltransferase, contributed to the transcriptional repression of microRNA-200 family members. Knockdown of EZH2 not only impacted H3K27 trimethylation but also reduced DNMT1 presence on the miR-200b/a/429 promoter. EZH2 appeared to be essential for DNMT1 recruitment to the promoter region. Silencing EZH2 and DNMT1 using drugs or RNA interference dramatically reduced the levels of miR-200b/a/429 expression. Collectively, these results indicated that EZH2 and DNMT1-mediated epigenetic silencing contributed to the progression of gastric cancer and glioblastoma, and therefore represents a novel therapeutic target for malignant tumors.

Ning X ，Shi Z ，Liu X ，Zhang A ，Han L ，Jiang K ，Kang C ，Zhang Q ... -  《-》