LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis

• Published in: Bioengineered Vol. 12; no. 2; pp. 10862 - 10877
• Main Authors: Zhou, Yongping, Li, Kuan, Zou, Xuexia, Hua, Zhiyuan, Wang, Hao, Bian, Wuyang, Wang, Hong, Chen, Fangming, Dai, Tu
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 20.12.2021
• Subjects: Animals; Apoptosis - genetics; Apoptosis Regulatory Proteins - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; DHRS4-AS1; Female; Gene Expression Regulation, Neoplastic - genetics; Hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Middle Aged; miR-522-3p; Oxidoreductases - genetics; proliferation; Research Paper; RNA, Long Noncoding - genetics; Signal Transduction - genetics; SOCS5; Suppressor of Cytokine Signaling Proteins - genetics; Hepatocellular carcinoma; DHRS4-AS1; miR-522-3p; proliferation; SOCS5
• ISSN: 2165-5979; 2165-5987
• DOI: 10.1080/21655979.2021.1994719

Recent years have seen much effect in revealing the pathological association between lncRNA and HCC. Herein, we identified lncRNA DHRS4-AS1 as a potential tumor suppressor in HCC. Firstly, it was discovered that DHRS4-AS1 was significantly down-regulated in HCC tissues compared to normal tissues based on the database TCGA. It was also detected in a lower-than-usual expression quantity in HCC tissues we collected and HCC cell lines. Kaplan-Meier survival analysis revealed that high expression of DHRS4-AS1 contributed to higher overall survival rate of HCC patients.DHRS4-AS1 expression was significantly correlated to tumor size (P = 0.02) and TNM stage (P = 0.045). CCK-8, BrdU and colony-forming assays collectively demonstrated that overexpression of DHRS4-AS1 significantly restrained HCC cell proliferation. In vivo xenograft animal experiment showed that DHRS4-AS1 could efficiently preclude the tumor growth of HCC. Further investigation performed using flow cytometry and western blot showed that DHRS4-AS1 exerted its effects by accelerating cell apoptosis and capturing cell cycle in G0/G1 phase. Our study subsequently lucubrated that miR-522-3p was a negative target of DHRS4-AS1. Increased expression level of miR-522-3p was examined in HCC tissues and cell lines. Similarly, miR-522-3p mimics could reverse the inhibitory effect on HCC brought by DHRS4-AS1. SOCS5 was then discovered as a down-stream target of miR-522-3p, which suggested that SOCS5 participated in DHRS4-AS1/miR-522-3p axis to collectively mediate the development of HCC. Our study provides lncRNA DHRS4-AS1/miR-522-3p/SOCS5 axis as a novel target for HCC therapeutic strategy with potentiality.