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RNF185-AS1 promotes hepatocellular carcinoma progression through targeting miR-221-5p/integrin β5 axis
Chunmei Huang1, Ke Li2, Rongfu Huang3
1Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Aims:
Recently, long noncoding RNAs (lncRNAs) have been reported to play important role in the pathogenesis of various cancers. However, the functions of RNF185-AS1 in hepatocellular carcinoma (HCC) remain unknown.
Materials And Methods:
The RNF185-AS1 expression in HCC cells and tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of RNF185-AS1 on tumor cell proliferation, migration and invasion were assessed by Cell Counting Kit-8 (CCK8) assay, colony formation assay, transwell assay. The luciferase reporter assay, RNA-binding protein immunoprecipitation assay, qRT-PCR and Western blot were performed to explore and confirm the interaction between RNF185-AS1 and miR-221-5p and integrin β5. The role of RNF185-AS1 in tumor progression was explored through in vivo experiments.
Key Findings:
RNF185-AS1 was highly expressed in HCC tissues and cell lines. High levels of RNF185-AS1 were correlated with advanced TNM stage, distant metastasis and a poorer overall survival rate. RNF185-AS1 knockdown inhibited cell proliferation, migration and invasion. Additionally, RNF185-AS1 acted as a sponge for miR-221-5p and integrin β5 was identified as a target gene of miR-221-5p. Rescue assays showed that miR-221-5p inhibitor or integrin β5 overexpression rescued the function of RNF185-AS1 knockdown on cell proliferation, migration, and invasion. Moreover, we found that RNF185-AS1 knockdown inhibited tumor growth and metastasis.
Significance:
Our study demonstrates that RNF185-AS1 is a new oncogenic lncRNA in HCC and suggests that the RNF185-AS1/miR-221-5p/integrin β5 axis might be a potential therapeutic target for HCC.
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