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微小RNA-146a-5p增强人参皂苷Rh2诱导的人肝癌细胞系HepG2的抗增殖作用及凋亡。

MicroRNA-146a-5p enhances ginsenoside Rh2-induced anti-proliferation and the apoptosis of the human liver cancer cell line HepG2.

作者信息

Chen Weiwen, Chu Shuai, Li Haixia, Qiu Yurong

机构信息

Medical Laboratories, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Medical Laboratories, Guangzhou Twelfth People's Hospital, Guangzhou, Guangdong 510620, P.R. China.

出版信息

Oncol Lett. 2018 Oct;16(4):5367-5374. doi: 10.3892/ol.2018.9235. Epub 2018 Jul 31.

Abstract

Liver cancer is one of the leading causes of malignancy-associated mortality worldwide and its clinical therapy remains very challenging. Ginsenoside Rh2 (Rh2) has been reported to have antitumor effects on some types of cancer, including liver cancer. However, its regulatory mechanism has not been extensively evaluated. In the present study, Rh2 increased the expression of microRNA (miR)-200b-5p, miR-224-3p and miR-146a-5p, and decreased the expression of miR-26b-3p and miR-29a-5p. Of the three upregulated miRs, miR-146a-5p exhibited the highest fold elevation. In accordance with a previous study, Rh2 effectively inhibited the survival of liver cancer cells and in a mouse model. In addition, it was observed that Rh2 markedly promoted liver cancer apoptosis and inhibited colony formation. Cell apoptosis and the inhibition of cell survival as well as colony formation induced by Rh2 were enhanced and weakened by miR-146a-5p overexpression and inhibition, respectively. The results of the present study provide further evidence of the antitumor effect of Rh2 in liver cancer and also demonstrate that this effect may be mediated via the regulation of miR-146a-5p expression in the liver cancer cell line HepG2. The results indicated that miR-146a-5p may be a promising regulatory factor in Rh2-mediated effects in liver cancer.

摘要

肝癌是全球恶性肿瘤相关死亡的主要原因之一,其临床治疗仍然极具挑战性。据报道,人参皂苷Rh2(Rh2)对包括肝癌在内的某些类型癌症具有抗肿瘤作用。然而,其调控机制尚未得到广泛评估。在本研究中,Rh2增加了微小RNA(miR)-200b-5p、miR-224-3p和miR-146a-5p的表达,并降低了miR-26b-3p和miR-29a-5p的表达。在这三种上调的miR中,miR-146a-5p的升高倍数最高。与先前的研究一致,Rh2在体外和小鼠模型中均有效抑制肝癌细胞的存活。此外,观察到Rh2显著促进肝癌细胞凋亡并抑制集落形成。miR-146a-5p的过表达和抑制分别增强和减弱了Rh2诱导的细胞凋亡以及对细胞存活和集落形成的抑制。本研究结果进一步证明了Rh2在肝癌中的抗肿瘤作用,并且表明这种作用可能是通过调节肝癌细胞系HepG2中miR-146a-5p的表达来介导的。结果表明,miR-146a-5p可能是Rh2介导的肝癌效应中有前景的调控因子。

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