Role of miR-143 and -145 in carcinogenesis of colon cancer

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We examined the expression levels of miRNAs (miRs) in colorectal tumors (63 cancer specimens and 65 adenoma specimens) and paired non-tumorous tissues. Decreased expression of miR-143 and -145 was frequently observed in the adenomas and cancers tested, compared with miR-34a down-regulation and miR-21 up-regulation. Expression profiles of miR-143 and -145 were not associated with any clinical features. Since the down-regulation of miR-143 and -145 was observed even in the early phase of adenoma formation, the decreased expression of both miRs would appear to contribute mainly to the initiation step of tumorigenesis, not to the progression stage, and not to clinical prognostic factors. For clinical application, we changed the sequences of the passenger strand in the miR-143 duplex and performed chemical modification at the 3'-overhang portion of miR-143, leading to greater activity and stability to nuclease. The cell growth inhibitory effect of the chemically modified synthetic miR-143 in vitro was greater than that of endogenous miR-143. The miR-143 showed a significant tumor-suppressive effect on xenografted tumors of DLD-1 human colorectal cancer cells.