Bioinformatic identification of miR-۴۶۴۵ hub target genes and experimental validation of the miR-۴۶۴۵ in breast cancer

Breast cancer is the most common cancer among women and is the second cancer frequently occurring worldwide.Both genetic and environmental factors play a role in breast cancer development.It has been shown that breast cancer is driven by epigenetic factors such as noncoding RNAs including miRNA.The miRNAs are small non-coding RNAs;regulate gene expression using RNA degradation or translation repression . miRNAs expression profiling was shown to be associated with tumor progression and response to therapy,suggesting their possible use as diagnostic, prognostic and predictive biomarkers .This study aimed to determine the relationship between miR-۴۶۴۵-۳p expression and clinical factors based on the qPCR data and regulatory mechanisms in breast cancer. Methods:twenty tumor and adjacent non-tumor sample breast tissues were examined in the study. hsa-miR۴۶۴۵-۳P levels were evaluated by qPCR in tumor tissues.For future explore of miRNA function, targets genes of miR-۴۶۴۵ were identified by the multiMiR package in R version ۴.۲.۱.Gene ontology and KEGG pathway analysis were accomplished to identify the biological function of miR-۴۶۴۵-۳P.APPI network was constructed to display key target genes.For hub genes validation,GEPIA databases were used.Results:miR-۴۶۴۵-۳P was downregulated in breast tumor tissues,and its reduction was significantly related to a poor prognosis in breast cancer.For identification of most pathways and genes,firstly ۵۱۶ target genes were predicted,KEGG pathway analysis proposed that target genes were enriched in long-term potentiation,glioma,ErbB signaling pathway,Oocyte meiosis, melanoma,and apoptosis.Finally,the ten hub genes(MAPK۱, MAP۲K۱,RHOA,JUN, ARRB۲,GNAQ,IGF۱R,TOP۲A, SMC۲,CEP۵۵)were detected from the PPI network.Conclusion:This study proposed that miR-۴۶۴۵-۳p down-regulation is associated with breast cancer progression and worse survival.

Keywords:

miR-۴۶۴۵ , Signaling pathway , Breast cancer , Overall survival