STAT1-induced regulation of lncRNA ZFPM2-AS1 predicts poor prognosis and contributes to hepatocellular carcinoma progression via the miR-653/GOLM1 axis

Author:

Zhang Xi-wu,Li Qiu-han,Xu Zuo-di,Dou Jin-jin

Abstract

AbstractLong noncoding RNAs (lncRNAs) have drawn growing attention owing to their important effects in various tumors, including hepatocellular carcinoma (HCC). Recently, a newly identified lncRNA, ZFPM2 antisense RNA 1 (ZFPM2-AS1), was reported to serve as an oncogene in gastric cancer. However, its function in tumors remains largely unknown. In this study, we identified ZFPM2-AS1 as a novel HCC-related lncRNA, which was observed to be distinctly upregulated in HCC tissues and associated with shorter overall survival. Luciferase reporter and chromatin immunoprecipitation assays suggested that overexpression of ZFPM2-AS1 was induced by STAT1. Functional investigations suggested that the inhibition of ZFPM2-AS1 suppressed cell proliferation, metastasis, cell cycle progression while accelerated cell apoptosis. Mechanistic studies showed that there were two binding sites of miR-653 within the sequence of ZFPM2-AS1 and the levels of ZFPM2-AS1 were negatively correlated with miR-653. In addition, ZFPM2-AS1 could reverse the suppressor effects of miR-653 on the proliferation and metastasis of HCC cells by the modulation of GOLM1, a target gene of miR-653. To conclude, we provided a better understanding of the interaction mechanism between ZFPM2-AS-miR-653-GOLM1 axis, which may help develop prognostic biomarkers and therapeutic target for HCC.

Funder

China Postdoctoral Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology

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