下咽癌中差异表达的蛋白激酶及其抑制剂的生物信息学筛选

doi:10.6040/j.issn.1673-3770.0.2015.340

摘要/Abstract

摘要： 目的筛选下咽癌中差异表达的激酶基因及其选择性抑制剂,为下咽癌的分子靶向治疗提供新的参考。方法利用GEO数据库和SAM软件筛选下咽癌中差异表达的激酶基因,体外培养人下咽癌FaDu细胞系。为验证GEO数据库中芯片结果的准确性,利用实时定量聚合酶链反应(Real-time PCR)检测差异表达激酶在FaDu细胞中的表达量,通过KEGG数据库获得激酶调控的通路,利用激酶抑制剂数据库和文献挖掘筛选获得在下咽癌FaDu细胞系中差异表达激酶的选择性抑制剂。结果 (1)在GEO数据库的下咽癌基因组表达谱中,共筛选出3个高表达的激酶基因,分别为PKC-β、CDK6和CDC42(差异倍数≥2.0且P<0.05);(2)Real-time PCR结果显示在人下咽癌FaDu细胞中这3个上调激酶基因也出现高表达(P<0.05),证明全基因组的结果准确;(3)KEGG通路分析的结果显示3个高表达激酶调控复杂的通路网络;(4)激酶抑制剂的筛选结果显示共有5个激酶抑制剂调控PKC-β, 4个激酶抑制剂调控CDK6,3个激酶抑制剂调控CDC42。文献挖掘的结果显示在这12个激酶抑制剂中,有4个在癌症方面的研究较少,文献<10篇。结论下咽癌中共有3个激酶PKC-β、CDK6和CDC42发生高表达,并发挥促癌作用。它们的激酶抑制剂可能有潜在的抗癌作用,为下咽癌的分子治疗提供新的切入点。

关键词: 下咽癌, 蛋白激酶, 激酶抑制剂, 生物信息学

Abstract: Objective To screen differentially expressed protein kinases and their inhibitors, in order to provide new targets for molecular therapy of hypopharyngeal cancer. Methods GEO database and SAM software were employed to screen the differentially expressed protein kinase genes in hypopharyngeal cancer. Human hypopharyngeal cancer FaDu cell line was cultured in vitro. Real-time PCR was used to prove the accuracy of microarray results. Based on KEGG database, the kinase-regulated pathways were identified. The inhibitors of such kinases were identified by using kinase-inhibitor database. Results A total of 3 protein kinase genes(PKC-β, CDK6 and CDC42)were identified(fold change≥2.0, P<0.05). Real-time PCR showed that the 3 kinase genes were differentially expressed in FaDu cells, which was consistent with the microarray results(P<0.05)Pathway analysis indicated that a complex pathway network was regulated by the 3 kinases. The results of inhibitor screening showed that 5 inhibitors regulated PKC-β, 4 inhibitors regulated CDK6 and 3 inhibitors regulated CDC42. There were less than 10 studies about the 4 inhibitors in cancer. Conclusion Three differentially expressed protein kinases(PKC-β, CDK6 and CDC42)are identified and they are able to promote the development of tumor. Their kinase inhibitors may play a potential anti-cancer role, which may provide a new target for molecular therapy of hypopharyngeal cancer.

Key words: Bioinformatics, Protein kinase, Kinase inhibitor, Hypopharyngeal cancer

中图分类号:

R739.65

胡文良,郑艳秋,崔晓波,崔彦茹,孙源昊. 下咽癌中差异表达的蛋白激酶及其抑制剂的生物信息学筛选[J]. 山东大学耳鼻喉眼学报, 2016, 30(3): 24-28.

HU Wenliang, ZHENG Yanqiu, CUI Xiaobo, CUI Yanru, SUN Yuanhao. Bioinformatic screening of differentially expressed protein kinases and their inhibitors in hypopharyngeal cancer.[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2016, 30(3): 24-28.

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