An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer

• Published in: Journal of applied genetics Vol. 60; no. 3-4; pp. 335 - 346
• Main Authors: Liu, Jiaxuan, Wang, Ping, Zhang, Ping, Zhang, Xinyu, Du, Hang, Liu, Qiang, Huang, Bo, Qian, Caiyun, Zhang, Shuhua, Zhu, Weifeng, Yang, Xiaohong, Xiao, Yingqun, Liu, Zhuoqi, Luo, Daya
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2019; Springer; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Antisense RNA; Bioinformatics; Biomarkers; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Carcinogenesis; Carcinogens; Care and treatment; Carrier Proteins - genetics; Computational Biology; Development and progression; Diagnosis; Diagnostic systems; DNA microarrays; Eukaryotic Translation Initiation Factor 5A; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Gene Regulatory Networks - genetics; Genes; Health aspects; Human Genetics; Human Genetics • Original Paper; Humans; Isoenzymes - genetics; L-Lactate Dehydrogenase - genetics; Life Sciences; MCF-7 Cells; Microbial Genetics and Genomics; MicroRNA; MicroRNAs - genetics; miRNA; Peptide Initiation Factors - genetics; Plant Genetics and Genomics; Regulators; Ribonucleic acid; RNA; RNA processing; RNA transport; RNA, Untranslated - genetics; RNA-Binding Proteins - genetics; Target recognition; Tumor cell lines; Tumor suppressor genes; Tumors; China; Breast cancer; Bioinformatics; miR-375; Biological pathway
• ISSN: 1234-1983; 2190-3883
• DOI: 10.1007/s13353-019-00507-w

MicroRNAs (miRNAs) are key regulators that play important biological roles in carcinogenesis and are promising biomarkers for cancer diagnosis and therapy. hsa-miR-375-3p (miR-375) has been suggested to serve as a tumor suppressor or oncogene in various tumor types; however, its specific expression and potential regulatory role in malignant breast cancer remain unclear. In this study, the results from noncoding RNA microarray analysis indicated that the miR-375 expression level is significantly decreased in malignant basal-like breast cancer compared with luminal-like breast cancer. A total of 1895 co-downregulated and 1645 co-upregulated genes were identified in miR-375 mimic-transfected basal-like breast cancer cell lines. Predicted miR-375 targets were obtained from the online databases TargetScan and DIANA-microT-CDS. Combined KEGG enrichment analysis for coregulated genes and predicted miR-375 targets provided information and revealed differences in potential dynamic signaling pathways regulated by miR-375 and also indicated specific regulatory pathways, such as RNA transport and processing, in basal-like breast cancer. Additionally, gene expression microarray analysis accompanied by UALCAN analysis was performed to screen upregulated genes in the basal-like subtype. Four potential key genes, including LDHB , CPNE8 , QKI , and EIF5A2 , were identified as candidate target genes of miR-375. Therefore, the present study demonstrated that miR-375 may be a potential key regulator and provide a promising direction for diagnostic and therapeutic developments for malignant breast cancer.