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| 二甲双胍通过miR-194-5p/RBM6通路抑制肝细胞癌细胞的恶性细胞表型的机制研究 | |
| 引用本文： | 王义刚,黄婷,汪俊州,唐荣幸,栗粟,熊勇. 二甲双胍通过miR-194-5p/RBM6通路抑制肝细胞癌细胞的恶性细胞表型的机制研究[J]. 河北医科大学学报, 2022, 43(12): 1371-1377+1427. DOI: 10.3969/j.issn.1007-3205.2022.12.002 |
| 作者姓名： | 王义刚 黄婷 汪俊州 唐荣幸 栗粟 熊勇 |
| 作者单位： | 1.四川省攀枝花市中心医院肝胆外科，四川 攀枝花 617000；2.四川省攀枝花市中心医院内分泌科，四川 攀枝花 617000 |
| 基金项目： | 攀枝花市级指导性科技项目（2020ZD-S-22） |
| 摘 要： | 目的 观察二甲双胍对肝细胞癌(hepatocellular carcinoma, HCC)细胞HepG2增殖、凋亡的影响，并探究其潜在机制与miR-194-5p/RNA结合基序蛋白6(RNA binding motif protein 6,RBM6)通路之间的关系。方法 随机将100例接受手术的HCC患者分为对照组、试验组，每组50例。对照组患者给予安慰剂口服，试验组给予二甲双胍口服。脂质体法将antagomiRNA、antagomiR-194-5p、pcDNA 3.1、pcDNA 3.1-RBM6、二甲双胍+si-NC、二甲双胍+si-RBM6、antagomiR-194-5p+si-NC、antagomiR-194-5p+si-RBM6转染至HepG2细胞。荧光定量聚合酶链式反应实验检测血清、组织、细胞中miR-194-5p、RBM6的表达；噻唑蓝法、5-溴-2-脱氧尿嘧啶染色检测细胞增殖；流式细胞术检测细胞凋亡；双荧光素酶报告基因实验检测细胞荧光活性；蛋白免疫印迹实验检测细胞RBM6蛋白。结果 试验组患者的2年无瘤生存期显著延长，患者治疗后血清miR-194-5p表达明显降低(P... |
| 关 键 词： | 肝肿瘤 二甲双胍 细胞凋亡 |
Mechanism of metformin inhibiting malignant cell phenotype of hepatocellular carcinoma cells through miR-194-5p/RBM6 pathway |
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| WANG Yi-gang,HUANG Ting,WANG Jun-zhou,TANG Rong-xing,LI Su,XIONG Yong. Mechanism of metformin inhibiting malignant cell phenotype of hepatocellular carcinoma cells through miR-194-5p/RBM6 pathway[J]. Journal of Hebei Medical University, 2022, 43(12): 1371-1377+1427. DOI: 10.3969/j.issn.1007-3205.2022.12.002 | |
| Authors: | WANG Yi-gang HUANG Ting WANG Jun-zhou TANG Rong-xing LI Su XIONG Yong |
| Affiliation: | 1.Department of Hepatobiliary Surgery, Panzhihua Central Hospital, Sichuan Province, Panzhihua 617000， China; 2.Department of Endocrinology, Panzhihua Central Hospital, Sichuan Province, Panzhihua 617000， China |
| Abstract: | Objective To observe the effect of metformin on the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells HepG2, and to explore the relationship between its potential mechanism and miR-194-5p/RNA binding motif protein 6 (RBM6) pathway.Methods A total of 100 patients with HCC undergoing surgery were randomly divided into control group and experimental group, with 50 cases in each group. The control group was given placebo orally and the experimental group was given metformin orally. Antigomirna, antigomiR-194-5p, pcDNA 3.1, pcDNA 3.1-RBM6, metformin+si-NC, metformin+si-RBM6, antigomiR-194-5p+si-NC and antigomiR-194-5p+si-RBM6 were transfected into HepG2 cells by liposome method. The expressions of miR-194-5p and RBM6 in serum, tissues and cells were detected by fluorescence quantitative polymerase chain reaction (FQ-PCR).MTT assay and 5-bromo-2-deoxyuracil staining were used to detect cell proliferation, and apoptosis was detected by flow cytometry. Double luciferase reporter gene assay was used to detect the fluorescence activity of cells, and RBM6 protein was detected by Western blot.Results The two-year disease-free survival (DFS) of the experimental group was significantly prolonged, and the expression of serum miR-194-5p decreased significantly after treatment (P＜0.05). In vitro cell study showed that the expression of miR-194-5p decreased, the proliferation ability decreased and the apoptosis ability increased significantly in HepG2 cells treated with metformin (P＜0.05). The expression of miR-194-5p in cancer tissues and HepG2 cells was significantly higher than that in adjacent tissues or normal hepatocytes. Inhibition of miR-194-5p weakened the proliferation and enhanced the apoptosis of HepG2 cells (P＜0.05). miR-194-5p negatively regulated the expression of RBM6. There was a significant negative correlation between miR-194-5p and RBM6 in hepatocellular carcinoma tissues (r=0.672, P＜0.05). Overexpression of RBM6 had a similar function with inhibition of miR-194-5p. Knockdown of RBM6 significantly inhibited metformin and the regulation of miR-194-5p on proliferation and apoptosis of HepG2 cells.Conclusion Metformin inhibits the proliferation of hepatocellular carcinoma cells, promotes apoptosis and improves DFS of patients. Its potential mechanism may be related to miR-194-5p/RBM6 pathway. |
| Keywords: | liver neoplasms metformin apoptosis |
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