Hsa-miR-125b在人胃癌耐药细胞株中的表达及其靶基因的功能分析

doi:10.3724/SP.J.1005.2014.0119

遗传 ›› 2014, Vol. 36 ›› Issue (2): 119-128.doi: 10.3724/SP.J.1005.2014.0119

Hsa-miR-125b在人胃癌耐药细胞株中的表达及其靶基因的功能分析

程燕^1,2, 陈琳³, 曹忻², 哈斯其美格², 谢小冬¹

1. 兰州大学基础医学院遗传学研究所, 兰州730000;
2. 西北民族大学实验中心, 兰州730030;
3. 兰州大学第一医院感染科, 兰州730000

收稿日期:2013-07-17 修回日期:2013-10-31 出版日期:2014-02-20 发布日期:2014-01-25
通讯作者: 谢小冬，教授，博士生导师，研究方向：少数民族的群体遗传和医学遗传。E-mail：xdxie@lzu.edu.cn E-mail:xdxie@lzu.edu.cn
作者简介:程燕，博士研究生，研究方向：肿瘤药物基因组学。E-mail：chengyanchina@qq.com
基金资助:
国家自然科学基金项目(编号：81272454，81071701)和西北民族大学中央高校基本科研业务费专项资金项目(编号：ZYZ2011105)资助

Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer

Yan Cheng^1,2, Lin Chen³, Xin Cao², Siqimeige Ha², Xiaodong Xie¹

1. Institute of Genetics, School of Basic Medical Science, Lanzhou University, Lanzhou 730000, China;
2. Experimental Center, Northwest University for Nationalities, Lanzhou 730030, China;
3. Department of Infectious Diseases, First Affiliated Hospital of Lanzhou University, Lanzhou 730000, China

Received:2013-07-17 Revised:2013-10-31 Online:2014-02-20 Published:2014-01-25

摘要/Abstract

摘要：

研究表明, Hsa-miR-125b在人胃癌耐氟尿嘧啶细胞株BGC823/Fu中表达下降。为进一步探讨hsa-miR-125b在获得性耐药中所起的作用, 文章应用miRbase、靶基因预测软件、Gene Ontology数据库及KEGG数据库对hsa-miR-125b的序列特征、进化保守性、靶基因及功能以及靶基因所参与的信号通路等进行了深入的生物信息学分析。结果显示：has-miR-125b在多个物种之间具有高度序列保守性; 通过软件预测获得hsa-miR- 125b 靶基因79个, 其分子功能包括转录调节、蛋白质结合和肽酶类活性等(P<0.001), 其所参与的生物学过程主要有细胞周期、细胞增殖、细胞凋亡的正性或负性调控以及细胞因子刺激反应性、药物反应性、DNA损伤反应性等(P<0.001), 调控包括MAPK、Wnt、p53等多条信号转导通路(P<0.01)。上述结果表明hsa-miR-125b可能参与调控多个生物学过程和信号转导通路, 而其中细胞增殖、细胞凋亡、细胞周期等生物学过程以及MAPK、Wnt、p53等信号通路已被证实与肿瘤耐药的发生有关。因此, hsa-miR-125b可能通过调控上述环节中的靶基因来影响肿瘤细胞对药物的敏感性, 从而为hsa-miR-125b在肿瘤耐药中的作用机制提供新的研究线索。

关键词: hsa-miR-125b, 生物信息学, 靶基因, 肿瘤化疗耐药, 胃癌

Abstract:

The expression of hsa-miR-125b is significantly downregulated in the fluorouracil-resistant cell line of human gastric cancer (BGC823/Fu). In order to investigate the role of hsa-miR-125b in the drug-resistance acquisition process of human gastric cancer, we performed a series of analysis on the sequence characteristics, species conservation, target genes, function annotation and signal transduction pathway enrichment of hsa-miR-125b using a combined bioinformatic approach such as miRbase, TargetScan6.2, PicTar, miRanda, Gene Ontology(GO) and KEGG. The results showed that the sequence of miR-125b is highly conserved in multiple species. A total of 79 target genes related to transcription regulation, protein binding, enzyme activity (P<0.001) were predicted by bioinformatics software. These genes involved in many biological processes including cell cycle, cell proliferation, cell apoptosis and cell responses to cytokine, drug responses and DNA damage (P<0.001). And these target genes mainly belong to MAPK, Wnt and p53 signal transduction pathways (P<0.01). The results revealed that hsa-miR-125b may regulate multiple biological processes and signal transduction pathways, and drug-resistant occurrence is associated with cell proliferation, cell apoptosis, cell cycle and signaling pathways including MAPK, Wnt and p53. We suggest that hsa-miR-125b may affect chemosensitivity by regulating target genes involved in the above processes and these target genes might be reliable candidates for exploring the role of hsa-miR-125b in tumor chemoresistance.

Key words: hsa-miR-125b, bioinformatics, target gene, chemotherapy resistance, human gastric cancer

程燕,陈琳, 曹忻, 哈斯其美格, 谢小冬. Hsa-miR-125b在人胃癌耐药细胞株中的表达及其靶基因的功能分析[J]. 遗传, 2014, 36(2): 119-128.

Yan Cheng, Lin Chen, Xin Cao, Siqimeige Ha, Xiaodong Xie. Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer[J]. HEREDITAS, 2014, 36(2): 119-128.

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Hsa-miR-125b在人胃癌耐药细胞株中的表达及其靶基因的功能分析

Expression profiling and functional analysis of hsa-miR-125b and its target genes in drug-resistant cell line of human gastric cancer

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