Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-beta receptor I kinase inhibitor (SD-208)

作者：Akbari Abolfazl; Ghahremani Mohammad Hossein; Mobini Gholam Reza; Abastabar Mahdi; Akhtari Javad; Bolhassani Manzar; Heidari Mansour^*

来源：Iranian Journal of Basic Medical Sciences, 2015, 18(9): 856-861.

• Colon cancer
• Oncogenic and suppressor
• micro RNAs (miRNAs)
• SD-208
• TGF-beta receptor 1 (TG beta RI)
• kinase inhibitor

Objective(s): Transforming growth factor-beta (TGF-beta) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-beta signaling. This work aims to show the effect of manipulation of TGF-beta signaling on some miRNAs implicated in CRC.
Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 mu M concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressormi-RNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-Delta Delta CT method through student's t-test via the GraphPad Prism software.
Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P= 0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b.
Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-beta inhibitors) may be owing to their ability to regulate miRNAs expression.

• 出版日期2015-9