Zhu Wen-Jing, Yan Ying, Zhang Jiu-Wei, Tang Yan-Dong, Han Bo
Abdominal Ultrasonic Department, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
Oncology Department, The First Hospital of Harbin, Harbin, Heilongjiang Province, People's Republic of China.
Cancer Manag Res. 2020 Apr 30;12:3013-3022. doi: 10.2147/CMAR.S237752. eCollection 2020.
This study aimed to investigate the effect and mechanism of miR-26a-5p on proliferation and apoptosis of hepatocellular carcinoma (HCC) cells.
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.
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.
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.
本研究旨在探讨miR-26a-5p对肝癌（HCC）细胞增殖和凋亡的影响及其机制。
采用RT-PCR分析HCC细胞中miR-26a-5p的表达，并通过生物信息学预测确定其靶向基因HMGA2 mRNA。通过MTT、侵袭和凋亡率检测，检测过表达miR-26a-5p的HCC细胞或敲低HMGA2表达后的细胞增殖、侵袭、凋亡率及相关蛋白表达水平。此外，促凋亡蛋白bax上调，抗凋亡相关蛋白Bcl-2下调。
RT-qPCR结果显示，HCC组织和细胞中miR-26a-5p水平下调，HMGA2表达上调；此外，miR-26a-5p与HMGA2的表达呈负相关；miR-26a-5p与肿瘤直径、分化程度、TNM分期及淋巴结转移相关。细胞实验证实miR-26a-5p具有肿瘤抑制作用，包括抑制两种肝癌细胞系的细胞增殖和侵袭并促进凋亡。生物信息学预测及后续实验证明HMGA2是miR-26a-5p的直接靶点；此外，敲低HCC细胞中HMGA2表达后，细胞增殖和侵袭能力明显受到抑制，凋亡率显著增加。
miR-26a-5p可通过直接靶向HMGA2抑制HCC细胞的增殖和侵袭并促进其凋亡。miR-26a-5p异常降低及其靶标HMGA2增加可能是参与HCC发生发展的重要因素。miR-26a-5p可能是其治疗的新潜在靶点。
