Down-regulation of miR-۱۳۵b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-۲۰۸)

  Objective(s):Transforming growth factor-β(TGF-β) is involved in colorectal cancer (CRC). The SD-۲۰۸ acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-۲۰۸ on SW-۴۸, a colon adenocarcinoma cell line. The cell line was treated with ۰.۵, ۱ and ۲ μM concentrations of SD-۲۰۸. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-۴۸ cell line into the nude mice. The animals were treated with SD-۲۰۸ for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-۲۱, ۳۱, ۲۰a and ۱۳۵b) and suppressor-miRNAs (let۷-g, miR-۱۳۳b, ۱۴۵ and ۲۰۰c). Data were analyzed using the ۲-∆∆CT method through student’s t-test via the GraphPad Prism software. Results: Our results revealed that SD-۲۰۸ could significantly down-regulate the expression of one key onco-miRNA, miR-۱۳۵b, in either SW-۴۸ colon cells (P=۰.۰۰۶) or tumors orthotopically implanted in nude mice (P=۰.۰۱۸). Our in silico study also predicted that SD-۲۰۸ could modulate the expression of potential downstream tumor suppressor targets of the miR۱۳۵b. Conclusion: Our data provide novel evidence that anticancer effects of SD-۲۰۸ (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression.

Keywords:

Colon cancer , Oncogenic and suppressor micro RNAs (miRNAs) , SD-۲۰۸ , TGF-β receptor ۱ (TGβRI) kinase inhibitor