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

Publish Year: 1394
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:

JR_IJBMS-18-9_002

تاریخ نمایه سازی: 3 آبان 1400

Abstract:

  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

Authors

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

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