结肠癌组织中microRNA表达谱的变化
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摘要
目的研究结肠癌组织中微小RNA(miRNA)表达谱的变化。方法收集5例结肠癌和5例癌旁组织进行miRNA基因芯片检测,从中筛选出异常表达的miRNA。通过生物信息学分析的方法对差异性表达miRNA所调控的靶基因、富集的生物过程和信号通路进行分析。结果通过Affymetrix miRNA4.0芯片检测,共筛选出73个差异性表达的miRNA,并对变化最明显的前13个上调及前13个下调的基因进行总结,其中包括hsa-miR-183-3p、hsa-miR-224-5p、hsa-miR-99a-5p等新的结肠癌相关基因。此外,生物信息学分析显示了差异性表达miRNA所调控的靶基因以及其所代表的生理意义,如蛋白质修饰过程、Wnt信号通路、癌症相关通路、翻译后蛋白质修饰、RAS信号通路、TP53转录调控等。结论检测结肠癌组织中miRNA表达谱的变化,对探讨结肠癌发病机制,寻找早期诊断和预后标志物,扩展治疗策略提供新的视野。
Objective To analyze the microRNA expression profile in Colon cancer. Methods 5 human colon cancer tissues and 5 peritumor normal tissues were collected for examining the microRNA expression changes by Affymetrix miRNA 4.0 microarray. Bioinformatics analysis was used to predict target genes of the deregulated microRNAs, identify the enriched pathways and biological processes of target gene. Results Gene expression profile analysis showed that 73 deregulated microRNA in colon cancer, the top 13 up-regulated and the top 13 down-regulated microRNAs were selected for a brief summary, including some novel colon cancer related genes, such as hsa-miR-183-3p,hsa-miR-224-5p,hsa-miR-99 a-5p. Moreover, bioinformatics analysis showed the physiological significance of predicted target genes of microRNA, such as protein modification process, Wnt signaling pathway, post translational protein modification, ras signaling pathway, pathways in cancer and TP53 transcriptional regulation.Conclusion Detection of changes in miRNA expression profiles in colon cancer tissues, providing new insights into the pathogenesis of colon cancer, finding early diagnostic and prognostic markers, and expanding treatment strategies.
Objective To analyze the microRNA expression profile in Colon cancer. Methods 5 human colon cancer tissues and 5 peritumor normal tissues were collected for examining the microRNA expression changes by Affymetrix miRNA 4.0 microarray. Bioinformatics analysis was used to predict target genes of the deregulated microRNAs, identify the enriched pathways and biological processes of target gene. Results Gene expression profile analysis showed that 73 deregulated microRNA in colon cancer, the top 13 up-regulated and the top 13 down-regulated microRNAs were selected for a brief summary, including some novel colon cancer related genes, such as hsa-miR-183-3p,hsa-miR-224-5p,hsa-miR-99 a-5p. Moreover, bioinformatics analysis showed the physiological significance of predicted target genes of microRNA, such as protein modification process, Wnt signaling pathway, post translational protein modification, ras signaling pathway, pathways in cancer and TP53 transcriptional regulation.Conclusion Detection of changes in miRNA expression profiles in colon cancer tissues, providing new insights into the pathogenesis of colon cancer, finding early diagnostic and prognostic markers, and expanding treatment strategies.
引文
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[2] Siegel R L, Miller K D, Jemal A. Cancer statistics, 2015 [J]. Ca-Cancer J Clin, 2015, 65(1): 5-29.
[3] D A SilvaF C, Wernhoff P, Dominguez-Barrera C, et al. Update on hereditary colorectal cancer [J]. Anticancer Res, 2016, 36(9): 4399-405.
[4] Hahn S, Jackstadt R, Siemens H, et al. SNAIL and miR-34a feed-forward regulation of ZNF281/ZBP99 promotes epithelial-mesenchymal transition [J]. EMBO J, 2013, 32(23): 3079-95.
[5] Ha M, Kim V N. Regulation of microRNA biogenesis [J]. Nat Rev Mol Cell Biol, 2014, 15(8): 509-24.
[6] Kohne C H. Successes and limitations of targeted cancer therapy in colon cancer [J]. Prog Tumor Res, 2014, 41:36-50.
[7] Gong J, Cho M, Fakih M. RAS and BRAF in metastatic colorectal cancer management [J]. J Gastrointest Oncol, 2016, 7(5): 687-704.
[8] Ozcan O, Kara M, Yumrutas O, et al. MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations [J]. Tumor Biol, 2016, 37(5): 6637-45.
[9] Zhang L, Huang L S, Chen G, et al. Potential targets and clinical value of MiR-224-5p in cancers of the digestive tract [J]. Cell Physiol Biochem, 2017, 44(2): 682-700.
[10] Han C, Zhou Y, An Q, et al. MicroRNA-1 (miR-1) inhibits gastric cancer cell proliferation and migration by targeting MET [J]. Tumor Biol, 2015, 36(9): 6715-23.
[11] Kent O A, Mendell J T, Rottapel R. Transcriptional regulation of miR-31 by oncogenic KRAS mediates metastatic phenotypes by repressing RASA1 [J]. Mol Cancer Res, 2016, 14(3): 267-77.
[12] Tsai T F, Lin J F, Chou K Y, et al. miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001-induced apoptosis in human urinary bladder urothelial carcinoma cells[J]. Onco Targets Ther, 2018, 11:239-52.
[13] Zhang C, Zhang C D, Ma M H, et al. Three-microRNA signature identified by bioinformatics analysis predicts prognosis of gastric cancer patients [J]. World J Gastroenterol, 2018, 24(11): 1206-15.
[14] Guinney J, Dienstmann R, Wang X, et al. The consensus molecular subtypes of colorectal cancer [J]. Nat Med, 2015, 21(11): 1350-6.
[15] Sokolova V, Fiorino A, Zoni E, et al. The Effects of miR-20a on p21: two mechanisms blocking growth arrest in TGF-beta-responsive colon carcinoma [J]. J Cell Physiol, 2015, 230(12): 3105-14.