miR-21的功能分析及其在结肠癌中的临床意义
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摘要
目的:分析miR-21的功能及其在结肠癌中的临床意义。方法:采用miRWalk在线工具预测和筛选miR-21的靶基因,并使用DAVID分析靶基因的功能和信号通路;检测结肠癌患者和健康对照人群血清以及癌组织和癌旁组织标本的miR-21的表达水平;使用TCGA数据库中结肠癌的数据,分析miR-21表达水平与临床病理参数的关系以及与患者预后的关系。结果:共筛选出429个miR-21的靶基因,靶基因功能分析提示这些基因主要参与了正性调节代谢过程、蛋白结合等。结肠癌患者血清miR-21表达水平显著高于健康对照人群,差异有统计学意义(P <0. 05)。TCGA数据显示,结肠癌组织中的miR-21表达水平与肿瘤的临床分期、肿瘤侵袭程度、淋巴结转移分期、远处转移分期无显著差异(P> 0. 05)。生存分析显示组织中高表达miR-21的患者其生存时间较低表达者短(P <0. 05)。结论:miR-21调控多个肿瘤发生相关的基因,在结肠癌发生过程中具有重要的调控作用。结肠癌患者miR-21表达水平显著高于健康人群,且miR-21高表达的患者预后差。
Objective: To analyze the function of miR-21 and the clinical significance in colon cancer. Methods:The target genes of miR-21 were screened by the miRWalk online tool,and the gene function and signal pathways were analyzed by DAVID tool. The serum levels of miR-21 were tested and compared in colon cancer patients and healthy controls. The data of colon cancer was download from TCGA database,and the relation of miR-21 with clinicopathological parameters were analyzed,the relation of miR-21 and prognosis of colon cancer patients was also analyzed. Results: 429 validated target genes of miR-21 were screened. These target genes were involving the positive regulation of metabolic process,protein binding. The serum levels of miR-21 were significantly increased in colon patients compared with that in healthy controls( P < 0. 05). The data of TCGA revealed that the expression of miR-21 in colon cancer tissue has not significant difference in clinical stage,tumor invasive,lymph node metastasis,distant metastasis of colon cancer( P > 0. 05). Survival analysis showed that high expression of miR-21 was associated with shorter survival time compared with low expression( P < 0. 05). Conclusion: miR-21 participate in the process of colon cancer by regulating several target genes. The expression of miR-21 was increased in colon patients compared with that in healthy controls,and high expression of miR-21 indicates a poor prognosis of colon cancer patients.
Objective: To analyze the function of miR-21 and the clinical significance in colon cancer. Methods:The target genes of miR-21 were screened by the miRWalk online tool,and the gene function and signal pathways were analyzed by DAVID tool. The serum levels of miR-21 were tested and compared in colon cancer patients and healthy controls. The data of colon cancer was download from TCGA database,and the relation of miR-21 with clinicopathological parameters were analyzed,the relation of miR-21 and prognosis of colon cancer patients was also analyzed. Results: 429 validated target genes of miR-21 were screened. These target genes were involving the positive regulation of metabolic process,protein binding. The serum levels of miR-21 were significantly increased in colon patients compared with that in healthy controls( P < 0. 05). The data of TCGA revealed that the expression of miR-21 in colon cancer tissue has not significant difference in clinical stage,tumor invasive,lymph node metastasis,distant metastasis of colon cancer( P > 0. 05). Survival analysis showed that high expression of miR-21 was associated with shorter survival time compared with low expression( P < 0. 05). Conclusion: miR-21 participate in the process of colon cancer by regulating several target genes. The expression of miR-21 was increased in colon patients compared with that in healthy controls,and high expression of miR-21 indicates a poor prognosis of colon cancer patients.
引文
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[4]Liang Z,Zhou HF.A review of microRNA-21 in colorectal cancer[J].Chinese Journal of Clinical Oncology,2014,41(24):1616-1618.[梁政,周慧芳.microRNA-21在结直肠癌中的研究进展[J].中国肿瘤临床,2014,41(24):1616-1618.]
[5]Chatterjee N,Rana S,Espinosa-Diez C,et al.MicroRNAs in Cancer:Challenges and opportunities in early detection,disease monitoring,and therapeutic agents[J].Curr Pathobiol Rep,2017,5(1):35-42.
[6]Jafri MA,Zaidi SK,Ansari SA,et al.MicroRNAs as potential drug targets for therapeutic intervention in colorectal cancer[J].Expert Opin Ther Targets,2015,19(12):1705-1723.
[7]Huang J,Furuya H,Faouzi M,et al.Inhibition of TRPM7 suppresses cell proliferation of colon adenocarcinoma in vitro and induces hypomagnesemia in vivo without affecting azoxymethane-induced early colon cancer in mice[J].Cell Commun Signal,2017,15(1):30.
[8]Liu YZ,Wang KQ,Ji DH,et al.Correlations of MC4R and MSH2expression with obesity in colon cancer patients[J].Eur Rev Med Pharmacol Sci,2017,21(9):2108-2113.
[9]Wang H,Nie L,Wu L,et al.NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21[J].Biochem Biophys Res Commun,2017,485(1):181-188.
[10]Liang Liang,Zhang Yinbin,Zhang Yang,et al.Mechanism of miR-21 affect cell viability and apoptosis in He La cells[J].Modern Oncology,2016,24(19):3005-3009.[梁亮,张寅斌,张扬,等.miR-21影响宫颈癌He La细胞生长和凋亡的机制探讨[J].现代肿瘤医学,2016,24(19):3005-3009.]
[11]Benoit YD,Laursen KB,Witherspoon MS,et al.Inhibition of PRC2 histone methyltransferase activity increases TRAIL-mediated apoptosis sensitivity in human colon cancer cells[J].J Cell Physiol,2013,228(4):764-772.
[12]De Simone V,Bevivino G,Sedda S,et al.Smad7 knockdown activates protein kinase RNA-associated e IF2αpathway leading to colon cancer cell death[J].Cell Death Dis,2017,8(3):e2681.
[13]Letellier E,Schmitz M,Ginolhac A,et al.Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence[J].Br J Cancer,2017,117(11):1689-1701.
[14]Conev NV,Donev IS,Konsoulova-Kirova AA,et al.Serum expression levels of miR-17,miR-21,and miR-92 as potential biomarkers for recurrence after adjuvant chemotherapy in colon cancer patients[J].Biosci Trends,2015,9(6):393-401.
[15]Liu J,Peng W,Wu ZH,et al.Plasma miR-21 expression in colon cancer patients before and after operation and its clinical significance[J].Cancer Research on Prevention and Treatment,2015,42(8):794-796.[刘洁,彭微,吴稚晖,等.结肠癌患者手术前后血浆miR-21表达水平变化及其临床意义[J].肿瘤防治研究,2015,42(8):794-796.]
[16]Iseki Y,Shibutani M,Maeda K,et al.Prognostic significance of microRNA-21 expression in patients with unresectable metastatic colon cancer[J].Anticancer Res,2016,36(10):5145-5151.