lncRNA GIHCG通过调节miR-429在原发性肝癌发生发展中的作用
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摘要
目的探讨lncRNA GIHCG通过调节miR-429在原发性肝癌发生发展中的作用。方法选择宁波市第七医院2017年1—12月60例原发性肝癌手术患者的肝癌组织及相应的癌旁组织。将HepG2细胞根据随机数字法分为空白对照组、阴性对照组和lncRNA GIHCG-siRNA组。采用RT-PCR测定肝癌组织和细胞中lncRNA GIHCG mRNA和miR-429水平,采用WST-1测定细胞增殖,采用Transwell法测定细胞侵袭和迁移能力。结果肝癌组织中lncRNA GIHCG mRNA水平高于癌旁组织(P<0.05),miR-429水平低于癌旁组织(P<0.05)。肝癌细胞中lncRNA GIHCG mRNA水平高于正常肝细胞(P<0.05),miR-429水平低于正常肝细胞(P<0.05)。肝癌组织及肝癌细胞中lncRNA GIHCG mRNA和miR-429呈负相关(P<0.05)。第3天和第5天,GIHCG-siRNA组细胞OD值低于空白对照组和阴性对照组(均P<0.05)。与空白对照组和阴性对照组比较,lncRNA GIHCG-siRNA组HepG2细胞中lncRNA GIHCG mRNA水平、细胞侵袭和迁移能力降低(均P<0.05),miR-429水平升高(均P<0.05)。结论原发性肝癌组织中lncRNA GIHCG水平升高,lncRNA GIHCG可能通过调节miR-429促进肝癌细胞增殖和侵袭迁移。
Objective To investigate the role of lncRNA GIHCG in the development of primary liver cancer by regulating miR-429. Methods The hepatocellular carcinoma and adjacent tissues of 60 cases of liver cancer in our hospital were prepared from January 2017 to December 2017. HepG2 cells were randomly divided into the blank control group, negative control group and lncRNA GIHCG-siRNA group with random number method. The levels of lncRNA GIHCG mRNA and miR-429 in the tissues and cells were determined by RT-PCR. The proliferations of cells were determined by WST-1. The invasion and migration ability of cells were determined by Transwell method. Results In the hepatocarcinoma tissues, the level of lncRNA GIHCG mRNA was higher than that in the adjacent tissues(P<0.05), however, the level of miR-429 was lower than that in the adjacent tissues(P<0.05). The level of lncRNA GIHCG mRNA of the liver cancer cells were higher than that of the normal hepatocytes(P<0.05), however, the level of miR-429 of the liver cancer cells were lower than that of the normal hepatocytes(P<0.05). There were negative correlation between lncRNA GIHCG mRNA and miR-429 in the liver cancer tissues and liver cancer cells(P<0.05). On D3 and D5, the OD value of cells in the GIHCG-siRNA group were lower than those in the blank control group and the negative control group(all P<0.05). When compared with the blank control group and the negative control group, the lncRNA GIHCG mRNA level, cell invasion and migration ability of the lncRNA GIHCG-siRNA group were decreased(all P<0.05), the miR-429 level was increased(all P<0.05). Conclusion The level of lncRNA GIHCG is elevated in primary liver cancer tissues, and lncRNA GIHCG may promote hepatoma cell proliferation and invasion and migration through regulating the expression of miR-429.
Objective To investigate the role of lncRNA GIHCG in the development of primary liver cancer by regulating miR-429. Methods The hepatocellular carcinoma and adjacent tissues of 60 cases of liver cancer in our hospital were prepared from January 2017 to December 2017. HepG2 cells were randomly divided into the blank control group, negative control group and lncRNA GIHCG-siRNA group with random number method. The levels of lncRNA GIHCG mRNA and miR-429 in the tissues and cells were determined by RT-PCR. The proliferations of cells were determined by WST-1. The invasion and migration ability of cells were determined by Transwell method. Results In the hepatocarcinoma tissues, the level of lncRNA GIHCG mRNA was higher than that in the adjacent tissues(P<0.05), however, the level of miR-429 was lower than that in the adjacent tissues(P<0.05). The level of lncRNA GIHCG mRNA of the liver cancer cells were higher than that of the normal hepatocytes(P<0.05), however, the level of miR-429 of the liver cancer cells were lower than that of the normal hepatocytes(P<0.05). There were negative correlation between lncRNA GIHCG mRNA and miR-429 in the liver cancer tissues and liver cancer cells(P<0.05). On D3 and D5, the OD value of cells in the GIHCG-siRNA group were lower than those in the blank control group and the negative control group(all P<0.05). When compared with the blank control group and the negative control group, the lncRNA GIHCG mRNA level, cell invasion and migration ability of the lncRNA GIHCG-siRNA group were decreased(all P<0.05), the miR-429 level was increased(all P<0.05). Conclusion The level of lncRNA GIHCG is elevated in primary liver cancer tissues, and lncRNA GIHCG may promote hepatoma cell proliferation and invasion and migration through regulating the expression of miR-429.
引文
[1] CROCETTI L,BARGELLINI I,CIONI R.Loco-regional treatment of HCC:current status[J].Clin Radiol,2017,72(8):626-635.
[2] CONG W M,WU M C.New insights into molecular diagnostic pathology of primary liver cancer:Advances and challenges[J].Cancer Lett,2015,368(1):14-19.
[3] CAI Z,XU K,LI Y,et al.Long noncoding RNA in liver cancer stem cells[J].Discov Med,2017,24(131):87-93.
[4] CHEN D,SUN Q,CHENG X,et al.Genome-wide analysis of long noncoding RNA (lncRNA) expression in colorectal cancertissues from patients with liver metastasis[J].Cancer Med,2016,5(7):1629-1639.
[5] D’ANIELLO C,PISCONTI S,FACCHINI S,et al.Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(5):1169-1170.
[6] 郭春梅,刘淑清,孙明忠.miR-429与肿瘤[J].中国生物化学与分子生物学报,2018,34(8):826-832.
[7] LI D,WANG H,SONG H,et al.The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells[J].Oncotarget,2017,8(49):85276-85289.
[8] MA L,WANG Q,GONG Z,et al.Long noncoding RNA GIHCG enhanced tongue squamous cell carcinoma progression through regulating miR-429[J].J Cell Biochem,2018,119(11):9064-9071.
[9] CHEN D L,LU Y X,ZHANG J X,et al.Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression[J].Theranostics,2017,7(19):4836-4849.
[10] WANG Y,HE L,DU Y,et al.The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling[J].Cell Stem Cell,2015,16(4):413-425.
[11] MOHANKUMAR S,PATEL T.Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer[J].Brief Funct Genomics,2016,15(3):249-256.
[12] WANG X,SUN W,SHEN W,et al.Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis[J].J Hepatol,2016,64(6):1283-1294.
[13] WANG Y,CHEN F,ZHAO M,et al.The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186[J].J Biol Chem,2017,292(37):15395-15407.
[14] HE Z H,QIN X H,ZHANG X L,et al.Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(1):46-54.
[15] SUI C J,ZHOU Y M,SHEN W F,et al.Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429[J].J Mol Med (Berl),2016,94(11):1281-1296.
[16] 王海兵,冯瑞庆,王庆锋.miR-429对食管鳞癌细胞EC9706的影响及其分子机制探讨[J].现代肿瘤医学,2018,26(20):3194-3199.
[17] WU C L,HO J Y,HUNG S H,et al.miR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome[J].Kaohsiung J Med Sci,2018,34(6):335-340.
[18] 刘棣,宋玲琴,张寅斌,等.胰腺癌患者血循环miR-429的表达及其临床意义[J].现代肿瘤医学,2018,26(15):2389-2392.
[19] SHENG N,ZHANG L,YANG S.MicroRNA-429 decreases the invasion ability of gastric cancer cell line BGC-823 by downregulating the expression of heparanase[J].Exp Ther Med,2018,15(2):1927-1933.
[20] NI J,YANG Y,LIU D,et al.MicroRNA-429 inhibits gastric cancer migration and invasion through the downregulation of specificity protein 1[J].Oncol Lett,2017,13(5):3845-3849.
[2] CONG W M,WU M C.New insights into molecular diagnostic pathology of primary liver cancer:Advances and challenges[J].Cancer Lett,2015,368(1):14-19.
[3] CAI Z,XU K,LI Y,et al.Long noncoding RNA in liver cancer stem cells[J].Discov Med,2017,24(131):87-93.
[4] CHEN D,SUN Q,CHENG X,et al.Genome-wide analysis of long noncoding RNA (lncRNA) expression in colorectal cancertissues from patients with liver metastasis[J].Cancer Med,2016,5(7):1629-1639.
[5] D’ANIELLO C,PISCONTI S,FACCHINI S,et al.Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(5):1169-1170.
[6] 郭春梅,刘淑清,孙明忠.miR-429与肿瘤[J].中国生物化学与分子生物学报,2018,34(8):826-832.
[7] LI D,WANG H,SONG H,et al.The microRNAs miR-200b-3p and miR-429-5p target the LIMK1/CFL1 pathway to inhibit growth and motility of breast cancer cells[J].Oncotarget,2017,8(49):85276-85289.
[8] MA L,WANG Q,GONG Z,et al.Long noncoding RNA GIHCG enhanced tongue squamous cell carcinoma progression through regulating miR-429[J].J Cell Biochem,2018,119(11):9064-9071.
[9] CHEN D L,LU Y X,ZHANG J X,et al.Long non-coding RNA UICLM promotes colorectal cancer liver metastasis by acting as a ceRNA for microRNA-215 to regulate ZEB2 expression[J].Theranostics,2017,7(19):4836-4849.
[10] WANG Y,HE L,DU Y,et al.The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling[J].Cell Stem Cell,2015,16(4):413-425.
[11] MOHANKUMAR S,PATEL T.Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer[J].Brief Funct Genomics,2016,15(3):249-256.
[12] WANG X,SUN W,SHEN W,et al.Long non-coding RNA DILC regulates liver cancer stem cells via IL-6/STAT3 axis[J].J Hepatol,2016,64(6):1283-1294.
[13] WANG Y,CHEN F,ZHAO M,et al.The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186[J].J Biol Chem,2017,292(37):15395-15407.
[14] HE Z H,QIN X H,ZHANG X L,et al.Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and therapeutic target for renal cell carcinoma[J].Eur Rev Med Pharmacol Sci,2018,22(1):46-54.
[15] SUI C J,ZHOU Y M,SHEN W F,et al.Long noncoding RNA GIHCG promotes hepatocellular carcinoma progression through epigenetically regulating miR-200b/a/429[J].J Mol Med (Berl),2016,94(11):1281-1296.
[16] 王海兵,冯瑞庆,王庆锋.miR-429对食管鳞癌细胞EC9706的影响及其分子机制探讨[J].现代肿瘤医学,2018,26(20):3194-3199.
[17] WU C L,HO J Y,HUNG S H,et al.miR-429 expression in bladder cancer and its correlation with tumor behavior and clinical outcome[J].Kaohsiung J Med Sci,2018,34(6):335-340.
[18] 刘棣,宋玲琴,张寅斌,等.胰腺癌患者血循环miR-429的表达及其临床意义[J].现代肿瘤医学,2018,26(15):2389-2392.
[19] SHENG N,ZHANG L,YANG S.MicroRNA-429 decreases the invasion ability of gastric cancer cell line BGC-823 by downregulating the expression of heparanase[J].Exp Ther Med,2018,15(2):1927-1933.
[20] NI J,YANG Y,LIU D,et al.MicroRNA-429 inhibits gastric cancer migration and invasion through the downregulation of specificity protein 1[J].Oncol Lett,2017,13(5):3845-3849.