Paper Information

Journal:   IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES   SEPTEMBER 2015 , Volume 18 , Number 9; Page(s) 856 To 861.
 
Paper: 

DOWN?REGULATION OF MIR-135B IN COLON ADENOCARCINOMA INDUCED BY A TGF?β RECEPTOR I KINASE INHIBITOR (SD-208)

 
 
Author(s):  AKBARI ABOLFAZL, GHAHREMANI MOHAMMAD HOSSEIN, MOBINI GHOLAMREZA, ABASTABAR MAHDI, AKHTARI JAVAD, BOLHASSANI MANZAR, HEIDARI MANSOUR*
 
* DEPARTMENT OF MEDICAL GENETICS, SCHOOL OF MEDICINE, TEHRAN UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
 
Abstract: 

Objective (s): Transforming growth factor? b (TGF? b) is involved in colorectal cancer (CRC). The SD?208 acts as an anti?cancer agent in different malignancies via TGF? b signaling. This work aims to show the effect of manipulation of TGF?? 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 mM 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 suppressormiRNAs (let7?g, miR?133b, 145 and 200c). Data were analyzed using the 2?DDCT 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? b inhibitors) may be owing to their ability to regulate miRNAs expression. Article history:

 
Keyword(s): COLON CANCER, ONCOGENIC AND SUPPRESSOR, MICRO RNAS (MIRNAS), SD?208, TGF?β RECEPTOR 1 (TGβRI), KINASE INHIBITOR
 
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