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

Bioengineered. 2021 Dec;12(2):10862-10877. doi: 10.1080/21655979.2021.1994719.

Abstract

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.

Keywords: DHRS4-AS1; Hepatocellular carcinoma; SOCS5; miR-522-3p; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Oxidoreductases / genetics*
  • RNA, Long Noncoding / genetics
  • Signal Transduction / genetics
  • Suppressor of Cytokine Signaling Proteins / genetics*

Substances

  • Apoptosis Regulatory Proteins
  • MIRN522 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SOCS5 protein, human
  • Suppressor of Cytokine Signaling Proteins
  • Oxidoreductases
  • DHRS4 protein, human

Grants and funding

We sincerely appreciated the assistance of Health Research Projects of Jiangsu Provincial Health Committee (H2019045) and the training program of ‘Double hundred’ young and middle-aged medical and health talents in Wuxi (BJ020034).