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Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma
Shuzhen Chang1, Binhe Chen2, Xiaoyan Wang1
1Division of Liver Disease, Ji'nan Infectious Disease Hospital, No. 22029 Jingshi Road, Ji'nan, Shandong, 250021, China.
Background:
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. This study was conducted to explore the effect of microRNAs on HCC metastasis.
Methods:
The 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.
Results:
MiR-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.
Conclusions:
MiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.
Insights
MicroRNA-181a promotes hepatocellular carcinoma (HCC) metastasis by targeting PTEN. This process is regulated by the long non-coding RNA XIST, impacting tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Hepatocellular carcinoma (HCC) metastasis significantly impacts patient prognosis.
- MicroRNAs (miRNAs) are recognized as key regulators in tumor metastasis.
Purpose of the Study:
- To investigate the role of specific microRNAs in HCC metastasis.
- To elucidate the molecular mechanisms underlying miRNA-mediated HCC metastasis.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to determine miR-181a levels in HCC tissues.
- Cell-based assays (CCK-8, wound-healing, Transwell) to assess proliferation and invasion.
- Bioinformatic analysis and luciferase assays to identify miR-181a targets and regulatory pathways.
Main Results:
- MiR-181a expression was significantly upregulated in HCC tissues, particularly in metastatic samples.
- PTEN was identified as a direct target gene of miR-181a.
- Long non-coding RNA XIST was found to mediate the regulation of PTEN by miR-181a, influencing cell proliferation and invasion.
Conclusions:
- MiR-181a promotes HCC metastasis through targeting PTEN.
- The lncRNA XIST plays a crucial role in the miR-181a/PTEN regulatory axis, driving HCC progression.