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通过抑制性消减杂交进行的基因组表达分析鉴定出人源神经保护因子(Humanin)的过表达,这是胃癌化疗耐药的一个靶基因。

Genome expression analysis by suppression subtractive hybridization identified overexpression of Humanin, a target gene in gastric cancer chemoresistance.

机构信息

Department of Pharmaceutical Biotechnology and Pharmaceutical Biotechnology Research Center, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran.

出版信息

Daru. 2014 Jan 8;22(1):14. doi: 10.1186/2008-2231-22-14.

Abstract

BACKGROUND

In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues.

RESULTS

In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166 ± 1.44 fold, was the most overexpressed isoform in GC.

CONCLUSIONS

The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer.

摘要

背景

在癌细胞中,细胞凋亡是影响化疗结果和化疗耐药性发展的重要机制。为了寻找与化疗耐药性和胃癌发展相关的基因,我们使用抑制差减杂交方法,鉴定出与正常胃组织相比在胃癌组织中过度表达的基因。

结果

在我们构建的抑制差减杂交文库中,过度表达最显著的基因是人源神经保护因子(humanin)异构体。人源神经保护因子是一种最近发现的内源性肽,具有抗凋亡活性,由于其在胃癌化疗耐药性中的潜在作用,被选为进一步研究的对象。通过实时定量 PCR 在临床样本中也观察到了人源神经保护因子异构体的上调。在所研究的异构体中,人源神经保护因子异构体 3 的表达水平上调了 4.166 ± 1.44 倍,是 GC 中过度表达最多的异构体。

结论

人源神经保护因子在胃癌中的过度表达提示其在化疗耐药性中的作用,并为胃癌的生物学特性提供了新的见解。我们提出人源神经保护因子异构体是对抗胃癌化疗耐药性的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e123/3896685/a1d11e5ab9ef/2008-2231-22-14-1.jpg

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