Colorectal cancer (CRC) is the second leading cause of death of malignant
tumors worldwide. Recent studies point to a role for the
adiponectin-receptor axis in colorectal
carcinogenesis, and in particular to the oncosuppressive properties of the
T-cadherin receptor. In addition, the loss of
T-cadherin expression in
tumor tissues has been linked to
cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of
microRNAs in CRC, this study explores their possible contribution to the downregulation of
T-cadherin. A systematic bioinformatics analysis, restricted by
microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top-ranking target
miRNA sites within the
3' UTR of
T-cadherin. Experimental validation analyses based on
luciferase reporter constructs and
miRNA mimic or
miRNA inhibitor transfections toward colorectal
adenocarcinoma cell lines indicated that miR-377-3p was able to directly bind to the
T-cadherin sequence, and thus downregulating its expression. Given the oncogenic activity of miR-377 and the oncosuppressive activity of
T-cadherin in CRC, the regulatory circuit highlighted in this study may add new insights into molecular mechanisms driving colorectal
carcinogenesis, and perspectively it could be exploited to identify novel
biomarkers and therapeutic targets.