Expression and Prognostic Value of miR-125b-5p in Lung Adenocarcinoma Based on Bioinformatics Analysis

Abstract

Abstract: Objective To analyze the expression of miR-125b-5p in lung adenocarcinoma (LUAD), and predict its target genes and prognostic value by bioinformatics analysis. Methods Tissue and cell chips of cisplatin resistance-related LUAD in Gene Expression Omnibus (GEO) database were obtained, and differentially expressed miRNAs were screened by R software. The miRBase database was used to analyze conservativeness, and the dbDEMC3.0 database was used to evaluate the expression level. The target genes were predicted by TargetScan, miRDB and miRTarBase databases, and were analyzed for functional term enrichment with the DAVID database. Combined with the survival information of LUAD patients in the Cancer Genome Atlas (TCGA) database, prognostic analysis was performed. Quantitative Real-time PCR (qRT-PCR) detection technology was used to detect the expression level of miR-125b-5p in human normal bronchial epithelial cell line 16HBE, LUAD cell line A549, and cisplatin-resistance cell line A549/DDP. Results miR-125b-5p, closely related to cisplatin resistant of LUAD, was obtained by analysis of the chip data. The sequence of miR-125b-5p was highly conserved among species, and miR-125b-5p was significantly down-regulated in various tumors including LUAD. Fifty-four target genes of miR-125b-5p were predicted. The results of enrichment analysis showed that the target genes of miR-125b-5p were mainly involved in the regulation of gene expression, cellular macromolecule biosynthetic process, and mainly enriched on MicroRNAs in cancer, Protein processing in endoplasmic reticulum, and HIF-1 signaling pathway. Survival analysis indicated that miR-125b-5p was significantly associated with poor prognosis of patients with LUAD. qRT-PCR results showed that the expression level of miR-125b-5p in A549 was significantly lower than in 16HBE (P=0.008). Compared to parental cell, the expression level of miR-125b-5p was significantly down-regulated in A549/DDP cell (P=0.023). Conclusion miR-125b-5p was abnormally expressed in LUAD, and its target genes involved in multiple biological processes and signal pathways, which might be used as a new biomarker for prognosis in LUAD.

Key words: bioinformatics, lung adenocarcinoma, cisplatin resistant, miR-125b-5p, prognosis

摘要： 目的应用生物信息学方法分析miR-125b-5p在肺腺癌（LUAD）中的表达,预测其靶基因及预后价值。方法选取GEO数据库中LUAD顺铂耐药组织和细胞芯片,应用R软件筛选差异表达miRNA。应用miRBase数据库进行保守性分析,并采用dbDEMC3.0数据库进行表达水平分析。利用TargetScan、miRDB、miRTarBase数据库预测靶基因,并运用DAVID在线网站对靶基因进行功能富集分析。联合TCGA数据库LUAD患者生存信息,进行预后分析。实时荧光定量PCR技术检测miR-125b-5p在人正常支气管上皮细胞系16HBE、LUAD细胞系A549以及顺铂耐药细胞系A549/DDP中的表达水平。结果分析芯片数据获得LUAD顺铂耐药相关miR-125b-5p,其具有高度保守性,并在LUAD中显著下调。预测到的54个靶基因主要富集在调节基因表达、细胞大分子生物合成等过程,以及MicroRNAs in cancer、Protein processing in endoplasmic reticulum、HIF-1 signaling pathway等通路。Kaplan-Meier生存分析结果提示,miR-125b-5p低表达与肺腺癌患者预后不良相关。qRT-PCR结果显示,miR-125b-5p在A549细胞中表达水平显著低于16HBE（P=0.008）;与亲本细胞相比,在耐药细胞A549/DDP中表达水平明显下降（P=0.023）。结论 miR-125b-5p在肺腺癌中表达异常,且其靶基因参与调控多个生物学过程及信号通路,可能是肺腺癌预后的生物标志物。

关键词: 生物信息学, 肺腺癌, 顺铂耐药, miR-125b-5p, 预后

CLC Number:

R734.2

GUO Na, XU Ying, LI Xiang-ling, WANG Peng, LI Lin, XU Qian, LIU Lei. Expression and Prognostic Value of miR-125b-5p in Lung Adenocarcinoma Based on Bioinformatics Analysis[J]. Journal of Chengde Medical University, 2022, 39(5): 365-370.

郭娜, 徐颖, 李祥伶, 王鹏, 李琳, 许倩, 刘镭. 基于生物信息学分析miR-125b-5p在肺腺癌中的表达及预后价值[J]. 承德医学院学报, 2022, 39(5): 365-370.

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