In silico analysis of hippo signaling pathway associated microRNAs in breast cancer

Abstract

Breast cancer (BC) is recognized as the leading cause of death among women worldwide. The hippo signaling pathway is a tumor-suppressive pathway, that regulates organ size, and cell regeneration. Dysregulation of the hippo pathway by the epigenetic modulator, noncoding RNAs (ncRNA) including microRNA(miR) promotes tumorigenesis through many cellular processes, including over proliferation, apoptosis resistance, and cell migration. This study aimed to identify aberrantly expressed miR, associated pathways, and targeted genes in BC. Data of mostly studied miRs were obtained from the miR Cancer database and PubMed. In addition pathway analysis and target prediction of scrutinized miRs were performed by DIANA miRPath v.3.Further functional and enrichment analyses of selected miRs were performed by Gene ontology(GO) annotation tool in DIANA miRPath v.3.Total nine hundred fifteen studies were included for analysis from which 54 mostly studied miRs were identified. Pathway enrichment analysis showed that among 54 miRs, 40 miRs have been significantly associated with core components of the hippo pathway (p-0.00049).i.e. Salvador Family WW Domain-Containing Protein (SAV1), Mammalian STE20-like 1/2(MST1/2), Mps One Binder Kinase Activator Protein 1(MOB1A/B), Large Tumor Suppressor Kinase 1/2 (LATS1/2), Yes-Associated Protein (YAP1), Transcriptional Coactivator With PDZ-binding Motif (TAZ), TEA Domain Transcription Factor (TEAD). The top nine miRs that were strongly associated with these genes have been selected from 40 miRs. I.e. hsa-miR-22-3p, hsa-miR-181a-5p, hsa-let-7a-5p, hsa-miR-34a-5p, hsa-miR-335-5p, hsa-miR-182-5p, hsa-miR-20a-5p, hsa-miR-27a-3p, hsa- miR-335-3p. These miRs play a very important role in apoptosis, tumor development and metastasis, and the prognosis of BC. Hence, the interaction of these miRs with the hippo pathway would modulate the molecular mechanism of the hippo signaling pathway. Thus, experimental studies are required to demonstrate the microRNAs and their targeted genes of the hippo signaling pathway, provide new research ideas for the treatment and diagnosis of BC.