LncRNA XIST regulates proliferation and migration of hepatocellular carcinoma cells by acting as miR-497-5p molecular sponge and targeting PDCD4

Yixi Zhang, Zebin Zhu, Shanzhou Huang, Qiang Zhao, Changjun Huang, Yunhua Tang, Chengjun Sun, Zhiheng Zhang, Linhe Wang, Huadi Chen, Maogen Chen, Weiqiang Ju, Xiaoshun He

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Background: MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. However, the relationship between miR-497-5p and HCC remains unclear. Methods: Kaplan-Meier curve analysis and the log-rank test were used to investigate the efficacy of miR-497-5p on overall survival (OS) and disease-free survival (DFS) in patients with HCC. According to in vitro experiments, programmed cell death 4 (PDCD4) was a target of miR-497-5p by the dual-luciferase activity assay. The efficacy of PDCD4 on cell proliferation and metastasis in HCC was examined by transwell assays, CCK-8 assays and reverse transcription quantitative PCR (RT-qPCR). Additionally, we conducted a luciferase activity reporter assay to confirm the interaction between lncRNA XIST and miR-49-5p. Then, to evaluate the relationship between lncRNA XIST and miR-497-5p, several mechanistic experiments, including qRT-PCR, Western blotting, transwell assays and tumor xenograft assays, were performed. Results: miR-497-5p was upregulated in HCC tissues, and high expression of miR-497-5p resulted in increases in tumor size and tumor number and a higher tumor-node-metastasis (TNM) stage and Edmondson grade in patients with HCC. Silencing miR-497-5p inhibited the proliferation and migration of HCC cells. PDCD4, which was downregulated in HCC tissues, was shown to be a target of miR-497-5p and was negatively correlated with the expression of miR-497-5p. lncRNA XIST was found to act as a miR-497-5p sponge and to regulate the level of PDCD4, which is targeted by miR-497-5p. lncRNA XIST was observed to be downregulated in the HCC tissues and positively correlated with the expression of PDCD4. Conclusions: Our findings reveal that the XIST/miR-497-5p/PDCD4 axis participates in HCC development and that XIST could be used as a biomarker of HCC.

Original languageEnglish (US)
Article number198
JournalCancer Cell International
Volume19
Issue number1
DOIs
StatePublished - Jul 29 2019

Keywords

  • Hepatocellular carcinoma
  • Migration
  • PDCD4
  • Proliferation
  • lncRNA XIST
  • miR-497-5p

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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