In recent years, exploring the potential of miRNAs as novel diagnostic, prognostic and diagnostic markers have gained much attention. In current study, we conducted an in-depth circRNA-miRNA-mRNA interactome to reveal significant molecular processes and biological pathways putatively associated with endometrial cancer (EC). Firstly, we retrieved two circRNAs from circad, hsa_circ_0002577 & hsa_circ_0109046, based on their association with the EC. Subsequently, we predicted miRNAs sponging sites in the two circRNAs and the potential target mRNAs of the predicted miRNAs. Sequestered miRNAs target a number of oncogenes (CBL, MET, KRAS), tumor suppressor (CFT R), receptor protein kinases & GT Pase (MET, KRAS, RAB1B), methyltransferases (SET D8), receptors associated factors (T RAF2, GRB2), growth factors (FGF20), autophagy (BECN1, AT G14), apoptotic regulators (BCL2), transcription factors (T Fs) (CREB1, RUNX1, RUNX2) and gene regulators (CCND1, HIF1A); and others, including some novel gene candidates (CREB1, FGF20, IFI27), that have never been implicated in EC earlier. The expression of hsa-miR-433-3p showed significant predictive relevance (Fold Change = 1.8, AUC = 0.736, Mann-Whitney test p-value = 6.1 e- 14) suggesting its predictive relevance in assessing patients' response to chemotherapy. The hsamiR- 188-3p targets autophagic and apoptotic regulators and its upregulation in endometriosis may be used as for the early stage diagnostic purpose. The hsa-miR-502-5p targets SET D8, T RAF2 and others and suggests additional genomic/epigenomic molecular targets for promising therapeutic interventions in EC. Predicted miRNAs target a number of mRNAs having varied functional impacts and offer an in-depth mechanistic insights for expatiating the biological and regulatory role in EC.Communicated by Ramaswamy H. Sarma.
Keywords: CircRNA-miRNA-mRNAs interactome; Endometrial cancer; diagnostic biomarkers; predictive biomarkers; prognostic biomarkers; signaling pathway.