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

Abstract

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

CLC Number:

R737.9

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.

References

[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.

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

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