Abolfazl Akbari - Colorectal Research Center, Rasoul-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
Mohammad Hossein Ghahremani - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Gholam Reza Mobini - Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
Mahdi Abastabar - Invasive Fungi Research Center, Department of Medical Mycology and Parasitology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Javad Akhtari - Immunogenetic Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Manzar Bolhassani - Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Mansour Heidari - Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

  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.

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