Effect and Mechanism of miR-26a-5p on Proliferation and Apoptosis of Hepatocellular Carcinoma Cells

Wen-Jing Zhu; Ying Yan; Jiu-Wei Zhang; Yan-Dong Tang; Bo Han

doi:10.2147/CMAR.S237752

Effect and Mechanism of miR-26a-5p on Proliferation and Apoptosis of Hepatocellular Carcinoma Cells

Cancer Manag Res. 2020 Apr 30:12:3013-3022. doi: 10.2147/CMAR.S237752. eCollection 2020.

Authors

Wen-Jing Zhu¹, Ying Yan², Jiu-Wei Zhang¹, Yan-Dong Tang³, Bo Han⁴

Affiliations

¹ Abdominal Ultrasonic Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
² Oncology Department, The First Hospital of Harbin, Harbin, Heilongjiang Province, People's Republic of China.
³ Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang Province, People's Republic of China.
⁴ Oncology Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

Abstract

Aim: This study aimed to investigate the effect and mechanism of miR-26a-5p on proliferation and apoptosis of hepatocellular carcinoma (HCC) cells.

Methods: RT-PCR was used to analyze the expression of miR-26a-5p in HCC cells and its targeted gene HMGA2 mRNA determined by biological information prediction. The rate of proliferation, invasion, apoptosis, and expression levels of related proteins of HCC cells overexpressing miR-26a-5p or those after knocking down HMGA2 expression were detected by MTT, invasion and apoptosis rate tests. Moreover, the apoptosis-promoting protein bax was upregulated and the anti-apoptosis-related protein Bcl-2 was downregulated.

Results: RT-qPCR results showed that the level of miR-26a-5p was downregulated in HCC tissues and cells, and the expression of HMGA2 was upregulated; besides, the expression of miR-26a-5p and HMGA2 was negatively correlated; miR-26a-5p was correlated with tumor diameter, differentiation degree, TNM staging and lymph node metastasis. Cell tests confirmed that miR-26a-5p functioned in tumor suppression, including inhibiting cell proliferation and invasion in two hepatocellular carcinoma cell lines and promoting apoptosis. Bioinformatics prediction and subsequent experiments proved that HMGA2 was the direct target of miR-26a-5p; moreover, after knocking down HMGA2 expression in HCC cells, cell proliferation and invasion ability were significantly inhibited, and apoptosis rate increased significantly.

Conclusion: miR-26a-5p can inhibit the proliferation and invasion of HCC cells and promote their apoptosis by directly targeting HMGA2. Abnormal decrease of miR-26a-5p and increase of its target HMGA2 are important factors that may participate in the occurrence and development of HCC. miR-26a-5p may be a new potential target for its treatment.

Keywords: apoptosis; hepatocellular carcinoma cells; mechanism research; miR-26a-5p; proliferation.