Identification of new biomarkers for cisplatin-resistance in A549 human lung adenocarcinoma cells by an integrated bioinformatical analysis
Identification of new biomarkers for cisplatin-resistance in A549 human lung adenocarcinoma cells by an integrated bioinformatical analysis
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通过综合生物信息分析鉴定 A549 人肺腺癌细胞顺铂耐药的新生物标志物
DOI：
10.21037/13972
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发表时间：
2017-06
影响因子：
0.9
通讯作者：
Jiang Guohui
中科院分区：
文献类型：
--
作者：
Wang Dong;Ma Leina;Ma Qingxia;Liu Jia;Jiang Guohui
背景：耐药是导致临床治疗失败的重要原因。本研究旨在寻找与人肺腺癌细胞顺铂耐药相关的关键基因。方法：从基因表达总表(GEO)数据库下载基因芯片数据集E-MEXP-3123和miRNA数据集GSE43249。对亲本和顺铂耐药的A549肺癌细胞的差异表达基因(Degs)和miRNAs(Dem)进行了鉴定。利用David数据库进行功能富集度分析和通径分析。通过Cytoscapp形成DEGS、microRNAs(MiRNAs)网络及其潜在的基因靶点之间的蛋白质-蛋白质相互作用。用实时定量聚合酶链式反应(qRT-PCR)验证顺铂耐药A549细胞中已鉴定的候选基因。结果：首先，从E-MEXP-3123中共鉴定出499个DEG。在基因本体论术语分析中，DEGS主要参与信号转导、氧化还原过程、多细胞生物体发育、细胞黏附和炎症反应。通路分析表明，最有意义的通路是神经活性配体-受体相互作用、内吞作用和河马信号通路。PPI网络分析显示，HUB基因的前5位分别是CDH1(钙粘蛋白1)、BDKRB2(缓激肽受体B2)、FPR2(甲酰肽受体2)、CCR5(C-C趋化因子受体5型)和YWHAE(酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白epsilon)。其次，从GSE43249中鉴定出12个DEM，排在前6位的DEM分别是miR-194、miR-192、miR-574-3p、miR-106b、miR-146a和miR-182。在随后的qRT-PCR实验中，与对照组相比，顺铂耐药组miR-192、miR-106b、miR-182低表达，miR-574-3p高表达。同时，实验还证实了miR-182潜在靶点NCALD、SPIN1的高表达和miR-574-3p潜在靶点PSMA4的弱表达。结论：本研究中发现的这些关键基因可能为在肺腺癌治疗中开发有效的抗顺铂耐药策略提供新的线索。
Background: Drug resistance plays an important role in the failure of clinical therapy. This study aimed to identify the key genes related to cisplatin resistance in A549 human lung adenocarcinoma cells. Methods: The mRNA microarray dataset E-MEXP-3123 and miRNA dataset GSE43249 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and miRNAs (DEMs) between parental and cisplatin-resistance A549 lung cancer cells were identified. Functional enrichment analysis and pathway analysis were performed by using the DAVID database. Protein-protein interactions of DEGs, microRNAs (miRNAs) network and their potential gene targets were formed by Cytoscape. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate the identified candidate genes in cisplatin-resistant A549 cells. Results: Firstly, a total of 499 DEGs were identified from E-MEXP-3123. In gene ontology (GO) term analysis, DEGs were significantly involved in signal transduction, oxidation-reduction process, multicellular organism development, cell adhesion and inflammatory response. Pathway analysis showed that the most significant pathways were neuroactive ligand-receptor interaction, endocytosis and hippo signaling pathway. PPI network showed that the top five hub genes were CDH1 (cadherin 1), BDKRB2 (bradykinin receptor B2), FPR2 (formyl peptide receptor 2), CCR5 (C-C chemokine receptor type 5) and YWHAE (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon). Secondly, 12 DEMs were identified from GSE43249, and the top six DEMs were miR-194, miR-192, miR-574-3p, miR-106b, miR-146a and miR-182. In subsequent qRT-PCR experiments, low expression levels of miR-192, miR-106b, miR-182 and high expression level of miR-574-3p were confirmed in cisplatin-resistant group compared with control group. Meanwhile as predicted, the overexpression of NCALD, SPIN1 that are miR-182 potential targets and the weak expression of PSMA4 that is miR-574-3p potential target were also experimentally validated in cisplatin-resistant lung cancer cells. Conclusions: These key genes identified in our study might provide new clues for developing effective strategies against cisplatin resistance during lung adenocarcinoma treatment.
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DOI：
10.1360/032013-305
发表时间：
2014-03
期刊：
--
影响因子：
--
作者：
Zhaoyong Xi;Yangzhong Liu
通讯作者：
Zhaoyong Xi;Yangzhong Liu
DOI：
10.1074/jbc.m109198200
发表时间：
2002-02
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Toshikazu Miyakawa;K. Obaru;K. Maeda;S. Harada;H. Mitsuya
通讯作者：
Toshikazu Miyakawa;K. Obaru;K. Maeda;S. Harada;H. Mitsuya
DOI：
10.3779/j.issn.1009-3419.2014.05.04
发表时间：
2014-05
期刊：
Zhongguo fei ai za zhi = Chinese journal of lung cancer
影响因子：
--
作者：
Zhang F;Li Y;Wu H;Qi K;You J;Li X;Zu L;Pan Z;Wang Y;Li Y;Li Y;Wang M;Shen W;Zhou Q
通讯作者：
Zhou Q
MiR-106b~25 簇通过下调 EP300 以不依赖 ABC 转运蛋白的方式调节多药耐药性。
影响因子：
4.2
作者：
Hu, Yunhui;Li, Kaiyong;Yaguee, Ernesto
通讯作者：
Yaguee, Ernesto
外泌体传输的 lncARSR 通过充当竞争性内源性 RNA 促进肾癌舒尼替尼耐药
影响因子：
50.3
作者：
Qu, Le;Ding, Jin;Wang, Lin-Hui
通讯作者：
Wang, Lin-Hui