生物信息学在三阴性乳腺癌miRNA生物标志物筛选中的应用

doi:10.13481/j.1671-587x.20190522

吉林大学学报(医学版) ›› 2019, Vol. 45 ›› Issue (05): 1098-1105.doi: 10.13481/j.1671-587x.20190522

• 基础研究 • 上一篇

生物信息学在三阴性乳腺癌miRNA生物标志物筛选中的应用

谭琦^1,2, 任立群³, 张祎冰³, 王亚帝², 谷泽慧^1,2, 黄鹏³, 陈素贤²

1. 锦州医科大学基础医学院病理学与病理生理学教研室, 辽宁锦州 121001;
2. 锦州医科大学附属第三医院病理科, 辽宁锦州 121001;
3. 吉林大学药学院实验药理与毒理学教研室, 吉林长春 130021

收稿日期:2019-02-20 发布日期:2019-10-08
通讯作者: 陈素贤,副教授,硕士研究生导师(Tel:0416-3999090,E-mail:csxsjpx@163.com) E-mail:csxsjpx@163.com
作者简介:谭琦(1993-),男,山东省潍坊市人,在读医学硕士,主要从事乳腺肿瘤基础和临床方面的研究。
基金资助:
辽宁省科技厅自然科学基金资助课题（2013022007）

Application of bioinformatics in screening of miRNA biomarkers in triple-negative breast cancer

TAN Qi^1,2, REN Liqun³, ZHANG Yibing³, WANG Yadi², GU Zehui^1,2, HUANG Peng³, CHEN Suxian²

1. Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou 121001, China;
2. Department of Pathology, Affiliated Third Hospital, Jinzhou Medical University, Jinzhou 121001, China;
3. Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun 130021, China

Received:2019-02-20 Published:2019-10-08

摘要/Abstract

摘要： 目的：通过医学癌症数据库（TCGA）和基因表达数据库（GEO）分析三阴性乳腺癌（TNBC）中差异表达微小RNA（miRNAs）并预测其靶基因，探讨其生物学功能和分子机制，寻找TNBC预后相关靶点。方法：下载TCGA数据库中343项关于乳腺癌组织与癌旁组织相关的miRNAs表达数据，筛选乳腺癌与癌旁组织中差异表达的miRNAs；GEO数据库验证miRNAs在TNBC细胞系的26种细胞株中的表达以及TNBC患者经过化疗前后血清中miRNAs的变化；通过基因本体（GO）功能注释及京都基因和基因组百科全书（KEGG）信号通路富集、蛋白质互作网络分析候选miRNAs的靶基因功能。结果： TCGA数据库，在乳腺癌组织中的miR-21-5p表达水平明显高于相邻癌旁组织（logFC=5.557，P<0.01）；GEO数据库筛选，miR-21-5p在TNBC细胞系中表达水平明显升高，在26种TNBC细胞株中超过20种细胞株相对表达水平>70 000，TNBC患者经联合化疗后miR-21-5p的表达水平明显降低（logFC=-5.07，P<0.01）；GO分析，miR-21-5p主要在DNA复制、转录以及血管重构等方面发挥调控作用；KEGG富集分析，miR-21-5p主要通过促分裂原活化蛋白激酶（MAPK）和转化生长因子β（TGF-β）等通路影响TNBC的发生发展。结论： miR-21-5p在TNBC组织中表达上调，在TNBC进展中发挥正调控作用，可能成为鉴定TNBC相关预后程度的关键生物学标志物。DUSP8等可能作为miR-21-5p的靶基因参与调控TNBC的发生发展。

关键词: miR-21-5p, 乳腺肿瘤, 三阴性乳腺癌, 生物信息学, 靶基因

Abstract: Objective:To analyze the differentially expressed miRNAs in triple negative breast cancer (TNBC) and predict their target genes through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, to explore their biological functions and molecular mechanisms, and to find the prognosis-related targets of TNBC. Methods:A total of 343 miRNAs expression data related to breast cancer tissue and adjacent tissue were downloaded from the TCGA database to screen the differentially expressed miRNAs in breast cancer and adjacent tissue. The GEO database was used to validate the expressions of miRNAs in 26 kinds of cell lines of TNBC and the changes in serum miRNAs in the TNBC patients before and after chemotherapy. The target gene function of candidate miRNAs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and protein interaction network. Results:The TCGA database showed that the expression level of miR-21-5p in breast cancer tissue was significantly higher than that in adjacent tissue (logFC=5.557, P<0.01). The results of GEO database showed that the expression level of miR-21-5p increased in TNBC cell line was significantly higher; the relative expression levels in more than 20 kinds of cell lines from 26 TNBC cell lines were over 70 000, and the expression level of miR-21-5p in the TNBC patients after combined chemotherapy was significantly decreased(logFC=-5.07, P<0.01).The GO analysis showed that miR-21-5p played a regulatory role in DNA replication, transcription and vascular remodeling. The KEGG enrichment analysis showed that miR-21-5p mainly affected the occurrence and development of TNBC through mitogen activated protein kinase(MAPK) and transforming growth factor-β(TGF-β) pathways. Conclusion:miR-21-5p is up-regulated in TNBC tissue and plays a positive regulatory role in the progression of TNBC, which may be a key biomarker for identifying the prognostic extent of TNBC. DUSP8 may be involved in the regulation of the occurrence and development of TNBC as a target gene of miR-21-5p.

Key words: miR-21-5p, breast neoplasms, triple negative breast cancer, bioinformatics, target genes

中图分类号:

R737.9

谭琦, 任立群, 张祎冰, 王亚帝, 谷泽慧, 黄鹏, 陈素贤. 生物信息学在三阴性乳腺癌miRNA生物标志物筛选中的应用[J]. 吉林大学学报(医学版), 2019, 45(05): 1098-1105.

TAN Qi, REN Liqun, ZHANG Yibing, WANG Yadi, GU Zehui, HUANG Peng, CHEN Suxian. Application of bioinformatics in screening of miRNA biomarkers in triple-negative breast cancer[J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1098-1105.

参考文献

[1] HARBECK N, GNANT M. Breast cancer[J].Lancet,2017,389(10074):1134-1150.
[2] DENKERT C, LIEDTKE C, TUTT A, et al. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies[J].Lancet,2017, 389(10087):2430-2442.
[3] 何江洋,李奉喜,黄垂国,等.胰腺癌特异性差异表达lncRNA相关的ceRNA调控网络的构建[J].郑州大学学报:医学版,2018,53(4):457-462.
[4] FABIAN M R, SONENBERG N, FILIPOWICZ W. Regulation of mRNA translation and stability by microRNAs[J]. Annu Rev Biochem, 2010, 79:351-379.
[5] LI X D, WU X F. MiR-21-5p promotes the progression of non-small-cell lung cancer by regulating the expression of SMAD7[J]. Onco Targets Ther, 2018, 11:8445-8454.
[6] GHORBANMEHR N, GHARBI S, KORSCHING E, et al. miR-21-5p, miR-141-3p, and miR-205-5p levels in urine-promising biomarkers for the identification of prostate and bladder cancer[J]. Prostate, 2019, 79(1):88-95.
[7] 何建林, 梅振宇, 盛勇,等. 三阴性乳腺癌新辅助治疗研究进展[J]. 中国肿瘤外科杂志, 2018, 10(5):330-332.
[8] HE Q, XUE S Y, TAN Y Q, et al. Dual inhibition of Akt and ERK signaling induces cell senescence in triple-negative breast cancer[J]. Cancer Lett, 2019, 448:94-104.
[9] FAN C, LIU N. Identification of dysregulated microRNAs associated with diagnosis and prognosis in triple-negative breast cancer:an in silico study[J]. Oncol Rep, 2019, 41(6):3313-3324.
[10] BHARDWAJ A, SINGH H, RAJAPAKSHE K, et al. Regulation of miRNA-29c and its downstream pathways in preneoplastic progression of triple-negative breast cancer[J]. Oncotarget, 2017, 8(12):19645-19660.
[11] MALLA R R, KUMARI S, GAVARA M M, et al. A perspective on the diagnostics, prognostics, and therapeutics of microRNAs of triple-negative breast cancer[J]. Biophys Rev, 2019, 11(2):227-234.
[12] PIASECKA D, BRAUN M, KORDEK R, et al. MicroRNAs in regulation of triple-negative breast cancer progression[J]. J Cancer Res Clin Oncol, 2018, 144(8):1401-1411.
[13] PEREZ-AÑORVE I X, GONZALEZ-DE LA ROSA C H, SOTO-REYES E, et al. New insights into radioresistance in breast cancer identify a dual function of miR-122 as a tumor suppressor and oncomiR[J]. Mol Oncol, 2019, 13(5):1249-1267.
[14] LI X H, CHEN D, LI M F, et al. The CADM2/Akt pathway is involved in the inhibitory effect of miR-21-5p downregulation on proliferation and apoptosis in esophageal squamous cell carcinoma cells[J]. Chem Biol Interact, 2018, 288:76-82.
[15] DAI J W, LIN Y Y, DUAN Y F, et al. Andrographolide inhibits angiogenesis by inhibiting the Mir-21-5p/TIMP3 signaling pathway[J]. Int J Biol Sci, 2017, 13(5):660-668.
[16] PARK S K, PARK Y S, AHN J Y, et al. MiR 21-5p as a predictor of recurrence in young gastric cancer patients[J]. J Gastroenterol Hepatol,2016,31(8):1429-1435.
[17] KOWALCZYK A E, KRAZINSKI B E, GODLEWSKI J, et al. SATB1 is down-regulated in clear cell renal cell carcinoma and correlates with miR-21-5p overexpression and poor prognosis[J]. Cancer Genomics Proteomics, 2016,13(3):209-217.
[18] YU W H, ZHU K X, WANG Y L, et al. Overexpression of miR-21-5p promotes proliferation and invasion of colon adenocarcinoma cells through targeting CHL1[J]. Mol Med, 2018,24(1):36.

生物信息学在三阴性乳腺癌miRNA生物标志物筛选中的应用

Application of bioinformatics in screening of miRNA biomarkers in triple-negative breast cancer

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