| 95 | 1 | 73 |
| 下载次数 | 被引频次 | 阅读次数 |
目的：探讨UBE2C在肝癌组织中的表达及沉默UBE2C后对肝癌细胞增殖和侵袭的影响。方法：从TCGA数据库中下载肝癌患者的数据集，分析肝癌组织中UBE2C mRNA的表达水平，按照肝癌组织中UBE2C mRNA中位表达水平，将所有肝癌患者分为高表达组(n=169)和低表达组(n=205)，分析与患者预后的关系，采用Cox回归分析肝癌预后的影响因素。选择人肝癌细胞系(HepG2、Huh7和SMMC-7721)和人肝上皮细胞系(THLE-3)，采用Western blot法和实时荧光定量PCR法检测4种细胞中UBE2C蛋白及mRNA的表达水平。HepG2细胞系中根据是否沉默UBE2C，分为空白对照组、空转NC组和si-UBE2C组。分析UBE2C基因沉默后对HepG2细胞增殖和侵袭的影响。结果：肝癌组织和癌旁正常肝脏组织中UBE2C mRNA表达水平分别为4.342(3.239,5.635)和0.905(0.587,1.230)，与癌旁正常肝脏组织相比，肝癌组织中UBE2C mRNA水平显著升高(P<0.001)；肝癌组织及配对癌旁正常肝脏组织中UBE2C mRNA表达水平分别为4.266(3.342,5.054)及0905(0.587,1.230)，与配对癌旁正常肝脏组织相比，肝癌组织中UBE2C mRNA水平显著升高(P<0.001)。肝癌组织UBE2C mRNA高表达组和低表达组中位生存时间为48.85个月和69.38个月，UBE2C mRNA高表达组中位生存时间显著缩短(P=0.045)。T分期(T3/T4)和UBE2C高表达是肝癌患者不良预后的独立危险因素(P<0.05)。相对于人肝上皮细胞系THLE-3,UBE2C蛋白和mRNA在人肝癌细胞系HepG2、Huh7和SMMC-7721中均显著高表达(P<0.05)，其中，UBE2C蛋白和mRNA在人肝癌细胞系HepG2表达最为显著。CCK-8结果显示，在72 h和96 h，与空白对照组和空转NC组相比，si-UBE2C组细胞增殖率显著降低，差异有统计学意义(P<0.05)。空白对照组、空转NC组和si-UBE2C组侵袭细胞数分别为(23.12±3.45)个、(24.33±2.83)个和(10.21±1.14)个，与空白对照组和空转NC组相比，si-UBE2C组侵袭细胞数显著降低，差异有统计学意义(P<0.05)。结论：UBE2C在肝癌组织中显著高表达，且UBE2C可作为肝癌患者不良预后的一项生物学标志物，UBE2C基因沉默后能显著抑制肝癌细胞系HepG2的增殖和侵袭。
Abstract：Objective:To investigate the expression level of UBE2C in liver cancer tissues and its effect on the proliferation and invasion of hepatocellular carcinoma cells HepG2 after UBE2C silencing.Methods:The data set of liver cancer was downloaded from the TCGA database.According to the median expression level of UBE2C mRNA in liver cancer tissues,all liver cancer patients were divided into UBE2C higher (n=169) and lower expression group (n=205),respectively.The expression level of UBE2C mRNA in liver cancer tissues and its relationship with the patients prognosis was analyzed.COX regression was used to analyze the influencing factors of the liver cancer patients prognosis.The human hepatocellular carcinoma cell lines(HepG2,Huh7 and SM M C-7721) and human nromal hepatic epithelial cell line (THLE-3) were selected,and the expression level of UBE2C in the four cell lines were detected by Western blot and real-time fluorescence quantitative PCR,respectively.The HepG2 cell line was protein and mRNA expression leves divided into control group,NC group and si-UBE2C group according to UBE2C silencing.The effects of UBE2C silencing on proliferation and invasion of HepG2 cell line were analyzed.Results:The expression level of UBE2C mRNA in liver cancer tissues and adjacent normal liver tissues were4.342 (3.239,5.635) and 0.905 (0.587,1.230),respectively.Compared with adjacent normal liver tissues,UBE2C mRNA levels in liver cancer tissues were significantly higher (P<0.001).The UBE2C mRNA expression levels in liver cancer tissues and paired adjacent normal liver tissues were 4.266(3.342,5.054) and 0905 (0.587,1.230),respectively.Compared with paired adjacent normal liver tissues,UBE2C mRNA expression levels in liver cancer tissues were significantly higher (P<0.001).The median survival time of UBE2C mRNA higher and lower expression groups was 48.85 months and 69.38 months.Compared with the lower expression group,the median survival time of UBE2C mRNA higher expression group was significantly shortened (P=0.045).T staging (T3/T4) and UBE2C expression (higher expression) were independent risk factors for poor prognosis in patients with liver cancer (P<0.05).Compared with human liver epithelial cell line THLE-3,UBE2C protein and mRNA were significantly higher expressed in human hepatocellular carcinoma cell line HepG2,Huh7 and SM M C-7721 (P<0.05).The expression level of UBE2C protein and mRNA expression was the most significant in human hepatocellular carcinoma cell line HepG2 relative to cell line Huh7 and SM M C-7721.The CCK-8 results show that the cell proliferation rate in si-UBE2C group were significantly decreased protein and mRNA expression levels compared to control group and NC group at 72 h and 96 h,and the differences were significant (P<0.05).The number of invasive cells in control group,NC group and si-UBE2C group were (23.12±3.45),(24.33±2.83) and(10.21±1.14),respectively.Compared with control group and NC group,the number of invasive cells in si-UBE2C group was significantly decreased (P<0.05).Conclusion:UBE2C was higher expressed in liver cancer,and can be used as a biomarker for poor prognosis of patients with liver cancer.After silencing of UBE2C gene can significantly inhibit proliferation and invasion of HepG2.
[1]谭妮，郑海平，欧超.肝癌根治术治疗原发性肝癌患者的术后生存率及预后影响因素分析[J].现代肿瘤医学，2019,27(5):826-829.
[2]陈靓，刘三海，黄强.NFAT5在肝细胞癌中表达的临床意义及其对IL-6、TNF-α表达的调控作用[J].中华内分泌外科杂志，2023,17(6):720-723.
[3]许珍，杨东昌，薛原，等.PDIA3在肝细胞肝癌中表达的临床意义及其对IL6、IL17表达的影响[J].中华内分泌外科杂志，2022,16(3):352-355.
[4] Xie C, Powell C, Yao M, et al. Ubiquitin-conjugating enzyme E2C:a potential cancer biomarker[J].Int J Biochem Cell Biol, 2014, 47:113-117.
[5]赵龙，张惠卿，王前，等.STMN1及UBE2C在胃癌组织中的表达及其临床意义[J].现代肿瘤医学，2021,29(7):1187-1191.
[6] Lu ZN, Song J, Sun TH, et al. UBE2C affects breast cancer proliferation through the AKT/mTOR signaling pathway[J].Chin Med J(Engl), 2021, 134(20):2465-2474.
[7] Liu Y, Zhao R, Chi S, et al. UBE2C is upregulated by estrogen and promotes epithelial-mesenchymal transition via p53 in endometrial cancer[J].Mol Cancer Res, 2020, 18(2):204-215.
[8] Yang YF, Chang YC, Tsai KW, et al. UBE2C triggers HIF-1α-glycolytic flux in head and neck squamous cell carcinoma[J].J Cell Mol Med, 2022, 26(13):3716-3725.
[9]郭星，魏震，王前，等.泛素偶联酶UBE2C在消化道肿瘤中的作用[J].中国现代普通外科进展，2021,24(10):800-804.
[10]于运亮，李婷，王莉莉，等.UBE2C和UBE2T与胰腺癌患者预后及免疫细胞浸润的关系[J].山东医药，2021,61(28):13-18.
[11] Wei Z, Liu Y, Qiao S, et al. Identification of the potential therapeutic target gene UBE2C in human hepatocellular carcinoma:An investigation based on GEO and TCGA databases[J].Oncol Lett,2019, 17(6):5409-5418.
[12]董文亮，刘洪涛，初侃，等.泛素偶联酶E2C在原发性肝癌中的表达及与临床病理参数和预后的关系[J].疑难病杂志，2020,19(10):994-998.
[13]刘梦，朱怡卿，黄金凤，等.泛素结合酶E2C通过特异性结合β-微管蛋白参与调控肝细胞癌进展[J].第二军医大学学报，2021,42(1):14-20.
[14]杨施晔，郭磊，冯锦凯，等.混合型肝癌预后评价及相关影响因素分析[J].中国实用外科杂志，2021,41(10):1168-1172.
[15]加静，朱超凡，艾绍庆.原发性肝癌患者介入治疗预后的影响因素分析[J].中国肿瘤临床与康复，2021,28(4):414-416.
[16] Morikawa T, Kawai T, Abe H, et al. UBE2C is a marker of unfavorable prognosis in bladder cancer after radical cystectomy[J].Int J Clin Exp Pathol, 2013, 6(7):1367-1374.
[17]许敏，薛栋，王黎昭，等.UBE2C表达对肝内胆管癌细胞增殖侵袭的影响及其预后评估价值[J].中国现代普通外科进展，2023,26(6):448-451,455.
基本信息:
DOI：
中图分类号:R735.7
引用信息:
[1]赵萍,庞丹,朱喜增等.UBE2C在肝癌中的表达及对HepG2细胞增殖和侵袭的影响[J].中国现代普通外科进展,2024,27(07):511-516.
基金信息:
河南省医学科技攻关计划项目（LHGJ20200905）