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

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

doi:10.1186/s12935-019-0909-8

Yixi Zhang, Shanzhou Huang + Show 11 more

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https://doi.org/10.1186/s12935-019-0909-8

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Abstract

BackgroundMicroRNAs (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.MethodsKaplan–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.ResultsmiR-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.ConclusionsOur 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.

Highlights

MicroRNAs play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC
MiR‐497‐5p was upregulated in HCC and could promote cell proliferation and migration in HCC Given the increased expression of miR-497-5p in the HCC tissues, we explored the expression levels of miR497-5p in HCC cell lines
We propose that the X inactive-specific transcript (XIST)/miR-497-5p/ programmed cell death 4 (PDCD4) axis participates in the development of HCC

Summary

Introduction

MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. Recent research has shown that the aberrant expression of noncoding RNAs (ncRNAs) is ubiquitous in different types of cancers, suggesting that ncRNAs play a key role in human carcinogenesis [9]. Growing evidence suggests that the abnormal expression of lncRNAs is implicated in a variety of diseases, including cancer [11,12,13], and that some tumor-associated lncRNAs play key roles in the development and metastasis of HCC [14,15,16]. LncRNA beta-Catm [16] is essential for the self-renewal of hepatocellular carcinoma stem cells and the proliferation of HCC tumors. By targeting the 3′-untranslated regions (UTRs) of mRNAs, the expression of the target gene can be regulated posttranscriptionally, thereby affecting the regulation of cell proliferation, differentiation and apoptosis [1]

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