利用 TCGA 数据库构建男性乳腺癌的lncRNA-miRNA-mRNA ceRNA 网络_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

章锐 , 祝孔俊 , 杜秋丽 , 袁媛 , 阮剑 ,  赵建国

武汉市第一医院甲状腺乳腺外科（武汉 430022）;

Corresponding author：

赵建国, Email: 3040114010@qq.com

Keywords：

男性乳腺癌; 长链非编码 RNA; 竞争内源性 RNA 网络; TCGA 数据库

DOI：

10.7507/1007-9424.202005027

Video：

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目的通过构建男性乳腺癌的竞争性内源 RNA（ceRNA）调控网络，探讨其发病机制。方法从 TCGA 数据库（The Cancer Genome Atlas Database）中下载男性乳腺癌的长链非编码 RNA（lncRNA）、微小 RNA（miRNA）和 mRNA 的表达谱数据，通过 R 软件的 limma 数据包分析男性乳腺癌差异表达的 lncRNA、miRNA 和 mRNA；分析三者之间的靶向调控关系，构建 ceRNA 网络，并用 Cytoscape 软件可视化，并将差异表达基因进行 GO 富集和 KEGG 通路分析。结果男性乳腺癌中差异表达的 lncRNA 为 275 种，差异表达的 miRNA 为 33 种，差异表达的 mRNA 为 1 675 种。本研究成功构建了男性乳腺癌的 lncRNA-miRNA-mRNA ceRNA 网络后，GO 富集分析显示，差异表达 mRNA 参与细胞增殖的负调控、转录的负调控、细胞蛋白质代谢过程的调控、细胞迁移的调控、转移酶活性的正调控、间充质细胞增殖的正调控等。KEGG 通路分析显示，差异表达 mRNA 参与癌症的途径、白细胞跨内皮迁移、丝裂原活化蛋白激酶（MAPK）和神经营养蛋白信号通路。结论本研究基于 TCGA 数据库成功构建了男性乳腺癌的 ceRNA 网络。

Citation： 章锐, 祝孔俊, 杜秋丽, 袁媛, 阮剑, 赵建国. 利用 TCGA 数据库构建男性乳腺癌的lncRNA-miRNA-mRNA ceRNA 网络. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(3): 380-384. doi: 10.7507/1007-9424.202005027 Copy

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28.	Cunliffe HE, Jiang Y, Fornace KM, et al. PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer. Am J Cancer Res, 2012, 2(5): 478-491.

1. Stang A, Thomssen C. Decline in breast cancer incidence in the United States: what about male breast cancer? Breast Cancer Res Treat, 2008, 112(3): 595-596.
2. White J, Kearins O, Dodwell D, et al. Male breast carcinoma: increased awareness needed. Breast Cancer Res, 2011, 13(5): 219.
3. Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment, and survivorship. Ann Oncol, 2013, 24(6): 1434-1443.
4. Falchetti M, Lupi R, Rizzolo P, et al. BRCA1/BRCA2 rearrangements and CHEK2 common mutations are infrequent in Italian male breast cancer cases. Breast Cancer Res Treat, 2008, 110(1): 161-167.
5. Silvestri V, Rizzolo P, Zanna I, et al. PALB2 mutations in male breast cancer: a population-based study in Central Italy. Breast Cancer Res Treat, 2010, 122(1): 299-301.
6. Young IE, Kurian KM, Annink C, et al. A polymorphism in the CYP17 gene is associated with male breast cancer. Br J Cancer, 1999, 81(1): 141-143.
7. Wasielewski M, den Bakker MA, van den Ouweland A, et al. CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat, 2009, 116(2): 397-400.
8. Huijts PE, Hollestelle A, Balliu B, et al. CHEK2*1100delC homozygosity in the Netherlands–prevalence and risk of breast and lung cancer. Eur J Hum Genet, 2014, 22(1): 46-51.
9. Sui J, Li YH, Zhang YQ, et al. Integrated analysis of long non-coding RNA-associated ceRNA network reveals potential lncRNA biomarkers in human lung adenocarcinoma. Int J Oncol, 2016, 49(5): 2023-2036.
10. Gennarino VA, D’Angelo G, Dharmalingam G, et al. Identification of microRNA-regulated gene networks by expression analysis of target genes. Genome Res, 2012, 22(6): 1163-1172.
11. Salmena L, Poliseno L, Tay Y, et al. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell, 2011, 146(3): 353-358.
12. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature, 2014, 505(7483): 344-352.
13. Zhou RS, Zhang EX, Sun QF, et al. Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue. BMC Cancer, 2019, 19(1): 779.
14. Chung HC, Kim DL, Koh EH, et al. Expression of prognostic factors (EGFR, ER) by immunohistochemical staining method in male breast cancer. Yonsei Med J, 1991, 32(2): 126-130.
15. Anderson WF, Jatoi I, Tse J, et al. Male breast cancer: a population-based comparison with female breast cancer. J Clin Oncol, 2010, 28(2): 232-239.
16. Murphy CE, Carder PJ, Lansdown MR, et al. Steroid hormone receptor expression in male breast cancer. Eur J Surg Oncol, 2006, 32(1): 44-47.
17. Ferreira M, Mesquita M, Quaresma M, et al. Prolactin receptor expression in gynaecomastia and male breast carcinoma. Histopathology, 2008, 53(1): 56-61.
18. 王蕾, 马佳康, 马军, 等. 利用GEO在线数据构建脑胶质母细胞瘤ceRNA网络. 中国实用神经疾病杂志, 2019, 22(11): 1168-1172.
19. Liu Z, Mi M, Li X, et al. lncRNA OSTN-AS1 may represent a novel immune-related prognostic marker for triple-negative breast cancer based on integrated analysis of a ceRNA network. Front Genet, 2019, 10: 850.
20. Song X, Zhang C, Liu Z, et al. Characterization of ceRNA network to reveal potential prognostic biomarkers in triple-negative breast cancer. PeerJ, 2019, 7: e7522.
21. Wang L, Luan T, Zhou S, et al. LncRNA HCP5 promotes triple negative breast cancer progression as a ceRNA to regulate BIRC3 by sponging miR-219a-5p. Cancer Med, 2019, 8(9): 4389-4403.
22. Cheng Y, Xiang G, Meng Y, et al. MiRNA-183-5p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting the PDCD4. Reprod Biol, 2016, 16(3): 225-233.
23. Liu H, Wang Y, Li X, et al. Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1. Tumour Biol, 2013, 34(3): 1713-1722.
24. Liu AN, Qu HJ, Gong WJ, et al. LncRNA AWPPH and miRNA-21 regulates cancer cell proliferation and chemosensitivity in triple-negative breast cancer by interacting with each other. J Cell Biochem, 2019, 120(9): 14860-14866.
25. Fang H, Xie J, Zhang M, et al. miRNA-21 promotes proliferation and invasion of triple-negative breast cancer cells through targeting PTEN. Am J Transl Res, 2017, 9(3): 953-961.
26. Zhang R, Zhang S, Xing R, et al. High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients. Thorac Cancer, 2019, 10(10): 1953-1961.
27. Liu B, Liu Y, Wang Y, et al. CyclinB1 deubiquitination by USP14 regulates cell cycle progression in breast cancer. Pathol Res Pract, 2019, 215(10): 152592.
28. Cunliffe HE, Jiang Y, Fornace KM, et al. PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer. Am J Cancer Res, 2012, 2(5): 478-491.

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利用 TCGA 数据库构建男性乳腺癌的lncRNA-miRNA-mRNA ceRNA 网络

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