Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression

Shuzhen Chang,Xiaoyan Wang,Keqin Wu,Yuqiu Sun,Binhe Chen

doi:10.1186/s12885-017-3216-6

Shuzhen Chang, Xiaoyan Wang + Show 3 more

Open Access

https://doi.org/10.1186/s12885-017-3216-6

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Abstract

BackgroundTumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis. This study was conducted to explore the effect of microRNAs on HCC metastasis.MethodsThe levels of miR-181a in HCC tissues, adjacent tissues, metastatic HCC tissues, and non-metastatic HCC tissues at different stages were determined by qRT-PCR. Effect of miR-181a on the proliferation, invasion, and metastasis of HCC cells was estimated by cell counting kits-8 (CCK-8), wound-healing, and Transwell assays. Software analysis and luciferase assays were used to explore the target gene of miR-181a.ResultsMiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST. The regulation of miR-181a on PTEN was mediated by lncRNA XIST. The proliferation and invasion of cells with siXIST were significantly enhanced compared with those of control cells, while knockdown of miR-181a abolished the enhancing effects.ConclusionsMiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.

Highlights

Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis
We investigated the molecular mechanism of miR-181a in the progression of Hepatocellular carcinoma (HCC) and the reciprocal regulation between miR-181a and the long non-coding RNA XIST
MiR-181a was up-regulated in HCC metastasis patients To explore whether and how miRNAs play key roles in HCC, miRNA data were downloaded from the database and uploaded to GEO to screen differentially expressed genes

Summary

Introduction

Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis. Hepatocellular carcinoma (HCC) is one of the most ubiquitous tumors in the world [1]. It grows rapidly and has a high propensity for metastasis, which worsens the prognosis of patients with this neoplasm [2]. HCC metastasis is a significant problem that needs to be addressed [3]. The molecular mechanisms by which HCC metastasis occurs are still unknown and need to be elucidated. Epithelial-to-mesenchymal transition (EMT) plays an important role in regulating metastasis and invasion by malignant tumors [4], including HCC [5].

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