An integrative bioinformatics analysis identified miR-375 as a candidate key regulator of malignant breast cancer
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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.
KeywordsBreast cancer miR-375 Bioinformatics Biological pathway
The authors would like to thank Qingmei Zhong, Xianhe Yang, Wu Wang, and Di Yao at Department of Pathology, Affiliated Infectious Diseases Hospital, Nanchang University, for their technical assistance.
DY.L., ZQ.L., and YQ.X. designed the experiments and reviewed paper; ZQ.L., JX.L., P.W., and Q.L. performed the dataset analysis; JX.L. and P.W. wrote the manuscript; CY.Q., SH.Z., WF.Z., and XH.Y. administered the cell models, qRT-PCR; P.Z., XY.Z., H.D., and B.H. carried out the immunohistochemistry. All authors reviewed and approved the final version.
This work was partially supported by National Natural Science Foundation of China (No. 81160248, 81360313, 81560464) (to Daya Luo and Zhuoqi Liu), Natural Science Foundation of Jiangxi Province (No. 20151BAB205058, 20171BAB205055) (to Daya Luo and Zhuoqi Liu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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