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结直肠癌中癌症相关基因及其调控性微小RNA的差异表达

Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma.

作者信息

Kara Murat, Yumrutas Onder, Ozcan Onder, Celik Ozgur Ilhan, Bozgeyik Esra, Bozgeyik Ibrahim, Tasdemir Sener

机构信息

Department of Medical Genetics, Faculty of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey.

Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.

出版信息

Gene. 2015 Aug 1;567(1):81-6. doi: 10.1016/j.gene.2015.04.065. Epub 2015 Apr 27.

DOI:10.1016/j.gene.2015.04.065
PMID:25925209
Abstract

Colorectal cancer is one of the frequently seen malignancies in the world. To date, several oncogenes and tumor suppressor genes have been identified and linked to colorectal cancer pathogenesis. Although recent advances in the diagnosis and therapy of colorectal cancer are promising, identifying novel genetic contributors is still high priority. In the present study, expression profile of some cancer-related genes and their regulatory miRNA molecules were evaluated by using a high-throughput real-time PCR method. For the study, a total of 54 patients diagnosed with CRC and normal colon tissue samples of 42 healthy controls were included. For the expression analysis, total RNA was extracted from FFPE tissue samples and converted to cDNA. All expression analyses were assessed by using Fluidigm Microfluidic Dynamic Array chips for 96 samples and the reactions were held in Fluidigm BioMark™ HD System Real-Time PCR. As a result of the study, expression of the ADAMTS1, FHIT, RUNX1, RUNX3 and WWOX genes was shown to be significantly altered in CRC tissues in contrast to normal tissue samples. Moreover, miR-378a-3p, miR-155-5p, miR-193b-3p, miR-96-5p, miR-17-5p, miR-27a-3p, miR-133b, miR-203a, miR-205-5p, miR-34c-5p, miR-130a-3p, miR-301a-3p, miR-132-3p, miR-222-3p, miR-34a-5p, miR-21-5p, miR-29a-3p and miR-29b-3p were found to be significantly deregulated in CRC. Consequently, results of the current study strongly suggest the involvement of novel cancer-related genes and their regulatory miRNAs in CRC physiopathology.

摘要

结直肠癌是世界上常见的恶性肿瘤之一。迄今为止,已鉴定出几种致癌基因和肿瘤抑制基因,并将其与结直肠癌的发病机制联系起来。尽管结直肠癌诊断和治疗方面的最新进展很有前景,但确定新的基因贡献者仍然是当务之急。在本研究中,使用高通量实时PCR方法评估了一些癌症相关基因及其调控miRNA分子的表达谱。该研究共纳入了54例诊断为结直肠癌的患者和42例健康对照的正常结肠组织样本。为了进行表达分析,从福尔马林固定石蜡包埋(FFPE)组织样本中提取总RNA并转化为cDNA。所有表达分析均使用Fluidigm微流控动态阵列芯片对96个样本进行评估,反应在Fluidigm BioMark™ HD系统实时PCR中进行。研究结果表明,与正常组织样本相比,ADAMTS1、FHIT、RUNX1、RUNX3和WWOX基因在结直肠癌组织中的表达有显著改变。此外,发现miR-378a-3p、miR-155-5p、miR-193b-3p、miR-96-5p、miR-17-5p、miR-27a-3p、miR-133b、miR-203a、miR-205-5p、miR-34c-5p、miR-130a-3p、miR-301a-3p、miR-132-3p、miR-222-3p、miR-34a-5p、miR-21-5p、miR-29a-3p和miR-29b-3p在结直肠癌中显著失调。因此,本研究结果强烈表明新的癌症相关基因及其调控miRNA参与了结直肠癌的生理病理学过程。

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