Exploring the Diagnostic Potential of miRNAs: A Comprehensive Analysis of miRNA Expression Profiles and Their Correlation with Target Genes in Colorectal Cancer

Abstract

Abstract Background: Recently studies reported that miRNAs play vital roles in pathogenesis of many human diseases including cancer, which may serve as diagnostic, prognostic markers and may provide means for cancer treatment. The study aimed to investigate the feasibility of using miRNAs as molecular markers for colorectal cancer detection. Methods: Paired tumour/normal tissues of 81 CRC patients were investigated to measure the expression level of six miRNAs (miR-20a, 21, 29a, 31, 92a and 224), evaluate mRNA and protein expressions in a further six genes (SMAD4, PTEN, TGFBRII, BCL2, KLF4 and RASA1) genes using RT-qPCR and immunohistochemistry analysis respectively. Results: In relative to the normal tissue mucosa, statistical analysis revealed a significant increase in the tumour expression level of (miR-20a (p=0.007), miR-21 (p=0.0003), miR-29a (p=0.001) and miR-31 (p=0.0003) with a decrease in the mRNA expression level of TGFBRII. Spearman’s rank order correlation demonstrated that high miR-20a expression was inversely correlated with PTEN-mRNA level (r= -0.238, p=0.033) and PTEN-protein level (r= -0.253, p= 0.023). High miR-21 and miR-224 expression were associated with low expression of TGFBRII-mRNA [(r= -0.358, p=0.001), (r= -0.276, p=0.013)] and TGFBRII-protein [(r= -0.328, p= 0.003), (r= -0.319, p=0.004)] respectively. In addition, over expression of both miR-29a and miR-31 inversely correlated with RASA1-mRNA level [(r= -0.217, p=0.014), (r= -0.276, p=0.013)] and RASA1-protein level [(r= -0.222, p=0.046), (r= -0.209, p=0.010)] respectively. Conclusions: The presence of a high degree of correlation between upregulated miRNAs and downregulation of some of target genes involved in different signalling pathways, indicated that miRNAs may have roles in CRC carcinogenesis. Additionally, upregulation of (miR-20a, 21, 29a and 31) may be suitable to differentiate CRC with a high degree of accuracy from a normal mucosa of CRC patients and can play a critical role on screening CRC in general population.