Xu Yongqing, Wang Helin, Gao Weike
Department of The Twelfth General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Arch Med Sci. 2019 Sep 12;16(6):1394-1401. doi: 10.5114/aoms.2019.87938. eCollection 2020.
Hepatic malignancy is one of the most common malignant neoplasms around the globe, and hepatocellular carcinoma (HCC) is the most common type. In this study, the roles and mechanisms of MiRNA-610 in the chemo resistance of HCC will be discussed.
The expression of MiRNA-610 and hepatoma-derived growth factor (HDGF) in HCC tissues and cell line was detected by quantitative real-time PCR. The proliferation and chemo resistance were analysed by MTT assay. Flow cytometry was used to examine the apoptosis rate. Luciferase reporter assay was used to verify the correlation between MiRNA-610 and HDGF. HDGF protein expression was detected by Western blot.
Our study confirmed the low-expression of MiRNA-610 in HCC tissues and cell line. Its low expression was related to high T stages and poor differentiation of HCC, and was a prognostic factor for HCC. MiRNA-610 upregulation inhibited cell proliferation and induced apoptosis of HepG2 cells. MiRNA-610 enhancement decreased the half maximal inhibitory concentration for cisplatin (DDP) and depressed the DDP resistance in HepG2 cells. The specific correlation between MiRNA-610 and HDGF was tested by luciferase reporter assay and western blot. The transfection with HDGF expression vector up-regulated the expression of HDGF protein silenced by MiRNA-610 enhancement. HDGF overexpression was found to reverse partly the regulatory roles of MiRNA-610 on malignancy and DDP resistance.
MiRNA-610 not only played a tumour suppressor role in HCC but also affected chemo resistance to DDP. This role is mainly mediated through targeted silencing of the HDGF gene, which may offer a new potential therapeutic target and improve the clinical therapeutic effect for HCC.
肝脏恶性肿瘤是全球最常见的恶性肿瘤之一，而肝细胞癌（HCC）是最常见的类型。在本研究中，将探讨微小RNA-610（MiRNA-610）在肝癌化疗耐药中的作用及机制。
采用定量实时聚合酶链反应检测肝癌组织及细胞系中MiRNA-610和肝癌衍生生长因子（HDGF）的表达。通过MTT法分析细胞增殖和化疗耐药情况。采用流式细胞术检测凋亡率。利用荧光素酶报告基因检测法验证MiRNA-610与HDGF之间的相关性。通过蛋白质免疫印迹法检测HDGF蛋白表达。
我们的研究证实了MiRNA- 在肝癌组织及细胞系中低表达。其低表达与肝癌的高T分期及低分化相关，是肝癌的一个预后因素。MiRNA-610上调可抑制细胞增殖并诱导HepG2细胞凋亡。MiRNA-610增强可降低顺铂（DDP）的半数最大抑制浓度，并降低HepG2细胞对DDP的耐药性。通过荧光素酶报告基因检测法和蛋白质免疫印迹法检测了MiRNA-610与HDGF之间的特异性相关性。转染HDGF表达载体可上调因MiRNA-610增强而沉默的HDGF蛋白表达。发现HDGF过表达可部分逆转MiRNA-610对恶性肿瘤和DDP耐药的调节作用。
MiRNA-610不仅在肝癌中发挥肿瘤抑制作用，还影响对DDP的化疗耐药性。这一作用主要通过靶向沉默HDGF基因介导，这可能为肝癌提供一个新的潜在治疗靶点并提高临床治疗效果。 610
