人表皮生长因子受体2阳性乳腺癌中差异表达的人表皮生长因子受体2相关长链非编码RNA-信使核糖核酸-微小核糖核酸竞争性内源RNA网络的构建
Construction of differentially expressed Her-2 related lncRNA-mRNA-miRNA ceRNA network in Her-2 positive breast cancer.
作者信息
Jia Xiaochen, Meng Wenjing, Zhang Lu, Jia Yongsheng, Shi Yehui, Tong Zhongsheng
机构信息
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
出版信息
Transl Cancer Res. 2020 Apr;9(4):2527-2533. doi: 10.21037/tcr.2020.03.34.
BACKGROUND
Her-2 positive subtype breast cancer is characterized as Her-2 gene amplification with poor survival and increased invasiveness accounting for 20-30% of invasive infiltrated breast cancer. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network is constructed to detect Her-2 specific RNAs in the development and progression of HER-2 positive breast cancer which may overcoming the anti-HER-2 therapy resistance of breast cancer cells.
METHODS
One thousand one hundred and nine breast cancer samples obtained from The Cancer Genome Atlas (TCGA) database were classified into two cohorts including ER+/PR+ (n=461) and ER-/PR- breast cancer (n=152). Differently expressed mRNAs, lncRNAs and miRNAs were screened in ER+/PR+ and ER-/PR- breast cancer cohorts, respectively. lncRNA-miRNA interactions were preformed to predicted and verified by miRcode. miRNA-mRNA interactions were selected to predict targeted mRNAs of miRNAs by miRanda, Targetscan and miRTarBase.
RESULTS
lncRNA-miRNA-mRNA ceRNA network was constructed by retained lncRNAs, miRNAs and mRNAs. Fifteen DEmiRNAs, 129 DElncRNAs and 269 DEmRNAs were retained in ER+/PR+ cohort after intersection with DEmiRNAs, DElncRNAs and DEmRNAs between breast cancer and normal tissues. Six hundred and ninety-three DEmRNAs, 25 DEmiRNAs and 364 DElncRNAs were retained in ER-/PR- cohort. ceRNA network in ER+/PR+ breast cancer cohort was constructed of the interactions of 4 DElncRNA-DEmiRNA pairs and 2 DEmiRNA-DEmRNA pairs included 4 DElncRNAs, 1 DEmiRNAs, and 2 DEmRNAs. ceRNA network in ER-/PR- breast cancer cohort was constructed of the interactions of 24 DElncRNA-DEmiRNA pairs and 1 DEmiRNA-DEmRNA pairs included 19 DElncRNAs, 4 DEmiRNAs, and 1 DEmRNA. MIR7-3HG- hsa-mir-204-NTRK2 axis was identified in both ER+/PR+ and ER-/PR- cohort in our study.
CONCLUSIONS
Based on the ceRNA hypothesis, a potential Her-2 related regulatory ceRNA networks are constructed which may provide novel insights into the mechanism underlying the biological processes of Her-2 positive breast cancer.
背景
人表皮生长因子受体2（Her-2）阳性亚型乳腺癌的特征是Her-2基因扩增，生存率低且侵袭性增加，占浸润性乳腺癌的20%-30%。构建长链非编码RNA（lncRNA）-微小RNA（miRNA）-信使核糖核酸（mRNA）竞争性内源RNA（ceRNA）网络，以检测Her-2阳性乳腺癌发生发展过程中的Her-2特异性RNA，这可能克服乳腺癌细胞的抗Her-2治疗耐药性。
方法
从癌症基因组图谱（TCGA）数据库获取的1109例乳腺癌样本被分为两个队列，包括雌激素受体（ER）阳性/孕激素受体（PR）阳性（n=461）和ER阴性/PR阴性乳腺癌（n=152）。分别在ER阳性/PR阳性和ER阴性/PR阴性乳腺癌队列中筛选差异表达的mRNA、lncRNA和miRNA。通过miRcode对lncRNA-miRNA相互作用进行预测和验证。通过miRanda、Targetscan和miRTarBase选择miRNA-mRNA相互作用，以预测miRNA的靶向mRNA。
结果
通过保留的lncRNA、miRNA和mRNA构建lncRNA-miRNA-mRNA ceRNA网络。在与乳腺癌和正常组织之间的差异表达miRNA、差异表达lncRNA和差异表达mRNA进行交集后，ER阳性/PR阳性队列中保留了15个差异表达miRNA（DEmiRNA）、129个差异表达lncRNA（DElncRNA）和269个差异表达mRNA（DEmRNA）。ER阴性/PR阴性队列中保留了693个DEmRNA、25个DEmiRNA和364个DElncRNA。ER阳性/PR阳性乳腺癌队列中的ceRNA网络由4对DElncRNA-DEmiRNA和2对DEmiRNA-DEmRNA的相互作用构建而成，包括4个DElncRNA、1个DEmiRNA和2个DEmRNA。ER阴性/PR阴性乳腺癌队列中的ceRNA网络由24对DElncRNA-DEmiRNA和1对DEmiRNA-DEmRNA的相互作用构建而成，包括19个DElncRNA、4个DEmiRNA和1个DEmRNA。在本研究中，ER阳性/PR阳性和ER阴性/PR阴性队列中均鉴定出MIR7-3HG-hsa-mir-204-NTRK2轴。
结论
基于ceRNA假说，构建了一个潜在的与Her-2相关的调控ceRNA网络，这可能为Her-2阳性乳腺癌生物学过程的潜在机制提供新的见解。
Zotero 插件