首页 | 本学科首页   官方微博 | 高级检索  
     


Concomitant Up-Regulation of Hsa- Mir-374 and Down-Regulation of Its Targets,GSK-3β and APC,in Tissue Samples of Colorectal Cancer
Authors:Mohammad Reza Bayatiani  Azam Ahmadi  Reza Aghabozorgi  Fatemeh Seif
Affiliation:1. Department of Radiotherapy and Medical Physics, Arak University of Medical Sciences, Arak, Iran. ; 2. Infectious Diseases Research Center (IDRC), Arak University of Medical Sciences, Arak, Iran. ; 3. Khansari Hospital and Department of Internal Medicine, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
Abstract:Background:The WNT-pathway is involved in several cancers, including colorectal cancer (CRC). Many cell signaling components and pathways are controlled by microRNAs. The main purpose of the present study was to investigate the expression of hsa-miR-374, and its two target genes of the Wnt-pathway in CRC clinical samples.Methods:In this study, we predicted the miRNAs targeting key genes of WNT-pathway using bioinformatics algorithms. The expression levels of hsa-miR-374, APC and GSK-3β on 48 pairs of Formalin-Fixed Paraffin-Embedded (FFPE) CRC tumors and marginal-tumors were evaluated using real time-PCR. Additionally, the hsa-miR-374a-5p precursor sequence was amplified by whole-blood DNA as a template. This amplicon was cloned into pEGFP-c1 expression vector and transfected into SW742 cells. Aside from this, MTT assay was performed to evaluate the effect of miR-374 on cell viability. Results:The bioinformatics analysis indicated that hsa-miR-374 binds to the regulatory region the key components of WNT-pathway, including APC and GSK-3β considering the recognition elements and mirSVR scores. Our results revealed significant down-regulation of GSK-3β (0.94 times, p= 0.0098) and APC (0.96 times, p= 0.03) and up-regulation of miR-374 (1.22 times, p= 0.0071) on tumor samples compared with their normal pairs. Meanwhile, the results of the over-expression of miR-374 showed down-regulation of APC and GSK-3β. MTT-assay also indicated that the miR-374 increased cell survival.Conclusion:The results of our study indicated a concomitant change in the expression of miR-374 and its two related target genes, in clinical samples of CRC. Hsa-miR-374 might be as a helpful biomarker or therapeutic target in CRC.Key Words: Colorectal cancer, GSK-3β, miR-374, WNT
Keywords:
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号