Abstract
AimsRecently, 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 methodsThe 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 findingsRNF185-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. SignificanceOur 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.
Highlights
Long noncoding RNAs have been reported to play important role in pathogenesis of various cancers
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, invasion and epithelial-mesenchymal transition (EMT)
Summary
Long noncoding RNAs (lncRNAs) have been reported to play important role in pathogenesis of various cancers. The function of RNF185-AS1 in hepatocellular carcinoma (HCC) metastasis has not been well investigated. The present study aims to explore the role and mechanism of RNF185-AS1 in hepatocellular carcinoma metastasis. The progress in the treatment of HCC has been made, high rate of metastasis and tumor recurrence is the main reason for the poor prognosis of HCC patients [1]. It is crucial to explore the molecular mechanisms in HCC recurrence and metastasis, so as to improve the treatment for HCC. LncRNA plays an important role in regulating various biological processes of tumor cell, including proliferation, differentiation, apoptosis, migration and invasion [3,4,5]. LINC00339 promote HCC cell proliferation and migration by sponging miR‐152 [8]
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