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

doi:10.1186/s12935-019-0909-8

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

Cancer Cell Int. 2019 Jul 29:19:198. doi: 10.1186/s12935-019-0909-8. eCollection 2019.

Authors

Yixi Zhang^#^{1

2

3}, Zebin Zhu^#^{1

2

3

4}, Shanzhou Huang^#^{1

2

3

5}, Qiang Zhao^{1

2

3}, Changjun Huang^{1

2

3}, Yunhua Tang^{1

2

3}, Chengjun Sun^{1

2

3}, Zhiheng Zhang^{1

2

3}, Linhe Wang^{1

2

3}, Huadi Chen^{1

2

3}, Maogen Chen^{1

2

3}, Weiqiang Ju^{1

2

3}, Xiaoshun He^{1

2

3}

Affiliations

¹ 1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Er Road, Guangzhou, 510080 China.
² 2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, China.
³ Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou, China.
⁴ 4Organ Transplant Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001 Anhui China.
⁵ Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

^# Contributed equally.

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.

Keywords: Hepatocellular carcinoma; Migration; PDCD4; Proliferation; lncRNA XIST; miR-497-5p.