Crosstalk in Tri-positive Cancer: Predictor and Diagnostic Mirnas in Focus

摘要

Cancer is a complex multifaceted disease caused by alterations at the genetic or epigenetic level in cells. Cancers in females majorly consist of ovarian, breast and cervical cancers, all of which, occurring concurrently, are referred to as 'Tri-positive cancer (TPC)'. Genetic and epigenetic mechanisms in TPC involve microRNAs; which are a class of endogenous, small, non-coding RNAs of 22 to 24 nucleotides that control gene expression. In TPC, upregulated oncogenic miRNAs includes: miR-21, miR-146a, miR-155, miR-182 and miR-200c while the downregulated tumour suppressor miRNAs includes: let-7b, miR-125b, miR-143 and miR-145. Cross-talk in TPC, which is the interaction between miRNAs and pathways, is an upshot of a complex network engaging the interplay of target genes such as PTEN, Muc-1, ERRB2/3, ZEB1/2, RAS, Bcl-2 and c-Myc among others, and occurring mostly through the P13k/Akt signaling pathway. Furthermore, an inverse relationship between miR-146a and miR-182, and BRCA gene with a direct relationship between miR-125b and BRCA gene was observed in the emergence of TPC. This review also showed that there are variations in the expression of let-7, miR-21, miR-125b and miR-200c between Tumour Initiating Cells (T-ICs) and TPC. Thus, since some of these miRNAs are dysregulated in chronic inflammations which play a critical role in tumourigenesis, proper investigation of these miRNAs and target genes in high risk individuals may aid prediction and early diagnosis of cancer and effective therapy with high reduction in mortality.