Yang Yang, Xing Yiqiao, Liang Chaoqun, Hu Liya, Xu Fei, Chen Yuan
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Tumour Biol. 2015 Jul;36(7):5571-9. doi: 10.1007/s13277-015-3227-3. Epub 2015 Feb 14.
This study aimed to screen potential microRNAs (miRNAs) and genes related to human primary breast cancer. The gene and miRNA expression profile data of GSE19783 was obtained from Gene Expression Omnibus. The matched messenger RNA (mRNA) and miRNA expression profiles of 100 human primary breast cancer samples were chosen for further analysis. The miRNA-gene regulatory modules were screened via iterative multiplicative updating algorithm. The potential functions of genes in modules were predicted by functional and pathway enrichment analysis; meanwhile, the potential functions of miRNAs were predicted by functional enrichment analysis. Furthermore, miRNA-miRNA functional synergistic network and miRNA-miRNA co-regulatory network were constructed. Totally, 16 miRNA-gene modules were screened, containing 222 miRNA-gene interactions. The genes in these modules were mainly related to breast cancer. Genes in module 6 (e.g., SFRP1) were enriched in cell junction assembly; genes in module 8 and 12 (e.g., ESR1 and ERBB4) were significantly implicated in mammary gland alveolus and lobule development. Meanwhile, genes in module 12 (e.g., ERBB4) were enriched in the pathway of endocytosis. Besides, several miRNAs (e.g., miR-375) were enriched in inflammatory cell apoptotic process; some other miRNAs (e.g., miR-139-5p and miR-9) were enriched in response to vitamin D. Additionally, miR-139-5p with several other miRNAs (e.g., miR-9) co-regulated SFRP1; miR-375, miR-592, and miR-135a co-regulated ESR1 and ERBB4. Some miRNAs (e.g., miR-139-5p and miR-9) and their target gene SFRP1, as well as several other miRNAs (e.g., miR-375, miR-592, and miR-135a) and their target genes (e.g., ESR1 and ERBB4), might be crucial in the pathogenesis of primary breast cancer.
本研究旨在筛选与人类原发性乳腺癌相关的潜在微小RNA（miRNA）和基因。从基因表达综合数据库中获取了GSE19783的基因和miRNA表达谱数据。选取100例人类原发性乳腺癌样本的匹配信使核糖核酸（mRNA）和miRNA表达谱进行进一步分析。通过迭代乘法更新算法筛选miRNA-基因调控模块。通过功能和通路富集分析预测模块中基因的潜在功能；同时，通过功能富集分析预测miRNA的潜在功能。此外，构建了miRNA-miRNA功能协同网络和miRNA-miRNA共调控网络。共筛选出16个miRNA-基因模块，包含222个miRNA-基因相互作用。这些模块中的基因主要与乳腺癌相关。模块6中的基因（如SFRP1）富集于细胞连接组装；模块8和12中的基因（如ESR1和ERBB4）显著参与乳腺腺泡和小叶发育。同时，模块12中的基因（如ERBB4）富集于内吞作用通路。此外，几种miRNA（如miR-375）富集于炎性细胞凋亡过程；其他一些miRNA（如miR-139-5p和miR-9）富集于对维生素D的反应。此外，miR-139-5p与其他几种miRNA（如miR-9）共同调控SFRP1；miR-375、miR-592和miR-135a共同调控ESR1和ERBB4。一些miRNA（如miR-139-5p和miR-9）及其靶基因SFRP1，以及其他几种miRNA（如miR-375、miR-592和miR-135a）及其靶基因（如ESR1和ERBB4）可能在原发性乳腺癌的发病机制中起关键作用。
