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MicroRNAs (miRNAs) play a crucial role in the process of coding gene expression, cells differentiation and cellular identity.
Emerging data suggests that miR-193a-3P and miR-451 play important roles in colorectal cancer by targeting KRAS and MIF
genes respectively. This study aimed to investigate the expression profiling of miR-193a-3P and miR-451 and identify the expression
level of their target genes in colorectal cancer tissues. A total of 60 fresh frozen human tissue specimens (matched cancer and noncancer
tissues) were used in this study. The expression pattern of miR-193a-3P and miR-451 in non-cancer tissue and primary cancer
was measured by using quantitative Real-Time PCR. The expression level of miR-193a-3P target gene (KRAS) and miR-451 target
gene (MIF) was assessed by immunohistochemical study. Also, the expression pattern of these miRNAs was correlated to different
pathological and clinical parameters. Majority of colorectal cancer tissues showed down regulation of miR-451 (83.3%) and miR-
193a-3P (68.3%) when compared to their matched non-cancer tissues. miR -193a-3P showed up regulation in 26.7% of the cases (fold
change ranged from 1.6 to 39.12). Low expression of miR-193a-3P showed significant correlation with early stages of tumor (stage I
and II) when compared to the advance stages (stage III and IV) (70.7%, n=29/41 versus 29.3%, n=12/41, P value=0.044). This study
showed significant correlation of miR-451down-regulation with recurrence of tumor and pre-existing adenoma when compared
to the high expression (26.0%, n=13/50 versus 0.0%, n=0/5, P value=0.013) (46.0%, n=23/50 versus 0.0%, n=0/5, P value<0.05)
respectively. Immunohistochemical study reveals more strong and moderate staining for MIF protein which is correlated inversely
with miR-451 down regulation (61.6% with moderate and strong staining versus 36.7% with low and null protein staining). Moreover,
down regulation of miR-451 was positively correlated with low miR-193a expression (p value=0.01). Furthermore, strong expression
pattern of MIF protein correlate positively with strong KRAS protein expression (p value=0.041). Dysregulation of miR-193a and
miR-451 in this study suggests that these miRNAs could play an important role in colorectal cancer pathogenesis. The significant
correlation between the expression patterns of these miRNAs and the significant correlation between their target genes (KRAS/MIF)
suggesting that there is interaction between the signaling pathways they involved. Additional studies with increase sample size and in
vitro studies are required to further validate the results.
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