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

Abstract

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.

• Authors: Jiaxuan Liu, Ping Wang, Ping Zhang, Xinyu Zhang, Hang Du, Qiang Liu, Bo Huang, Caiyun Qian, Shuhua Zhang, Weifeng Zhu, Xiaohong Yang, Yingqun Xiao, Zhuoqi Liu, Daya Luo
• Journal: Journal of applied genetics (J Appl Genet) Vol. 60 Issue 3-4 Pg. 335-346 (Nov 2019) ISSN: 2190-3883 [Electronic] England
• PMID: 31372832 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CPNE8 protein, human
• Carrier Proteins
• Isoenzymes
• MIRN375 microRNA, human
• MicroRNAs
• Peptide Initiation Factors
• QKI protein, human
• RNA, Untranslated
• RNA-Binding Proteins
• L-Lactate Dehydrogenase
• lactate dehydrogenase 1

Topics

• Biomarkers, Tumor (genetics)
• Breast Neoplasms (genetics, pathology)
• Carrier Proteins (genetics)
• Computational Biology
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Gene Regulatory Networks (genetics)
• Humans
• Isoenzymes (genetics)
• L-Lactate Dehydrogenase (genetics)
• MCF-7 Cells
• MicroRNAs (genetics)
• Peptide Initiation Factors (genetics)
• RNA, Untranslated (genetics)
• RNA-Binding Proteins (genetics)
• Eukaryotic Translation Initiation Factor 5A