非小细胞肺癌细胞A549顺铂耐药潜在机制的全转录组测序分析

Potential mechanism of cisplatin resistance in non-small cell lung cancer A549 cells analyzed by the whole-transcriptome

目的通过全转录组测序分析比较野生型A549细胞和顺铂耐药A549细胞(A549/DPP)表达谱的差别,揭示非小细胞肺癌(NSCLC)顺铂耐药潜在机制。方法首先建立A549/DDP细胞系,对A549和A549/DDP进行全转录组测序,分别对lnc RNA-seq,circ RNA-seq和mi RNA-seq数据进行差异表达以及功能富集分析(KEGG和GO分析)。然后进行全转录组数据联合分析以及ce RNA网络的构建。结果与A549细胞系相比,其中4517个lnc RNA、123个circ RNA以及145个mi RNA在A549/DDP细胞中有差异表达。显著富集在与癌症相关的通路上。mi RNA-circ RNA-lnc RNA-m RNA四元网络包含了12个mi RNA,4个circ RNA,23个lnc RNA和9个m RNA节点。经过拓扑学性质分析hsa-mi R-125a-5p和hsa-mi R-125b-5p是顺铂耐药相关的关键mi RNA。结论肿瘤坏死因子信号通路和p53信号通路参与了A549/DPP耐药机制。Hsa-mi R-125a-5p和hsa-mi R-125b-5p可能是逆转顺铂抗性的潜在靶点。

Objective To reveal the potential mechanism of cisplatin resistance in non-small cell lung cancer A549 cells by comparing the expression profiles of wild-type A549 cells and cisplatin-resistant A549 cells(A549/DPP)through whole transcriptome sequencing analysis.Methods The cisplatin resistant A549(A549/DDP)cell line was first established.Then,the whole-transcriptome analysis was conducted both on A549 and A549/DDP cells.Next,the differentially expressed RNAs of lnc RNA-seq,circ RNA-seq,and mi RNA-seq data were identified,respectively,followed by functional enrichment analysis.Finally,a comprehensive analysis based on the whole transcriptome data was performed and the construction of the ce RNA network was carried out.Results A total of 4517 lnc RNA,123 circ RNA,and 145 mi RNA were differentially expressed in A549/DDP cells compared with the A549 cell line.These different RNAs were significantly enriched in cancer-related pathways.The ce RNA network contained 12 mi RNAs,4 circ RNAs,23 lnc RNAs,and 9 m RNA nodes,of which hsa-mi R-125 a-5 p and hsa-mi R-125 b-5 p were important mi RNAs based on the topological analysis.Conclusion Tumor necrosis factor signaling pathway and p53 signaling pathway are involved in A549/DPP resistance.Hsa-mi R-125 a-5 p and hsa-mi R-125 b-5 p may be potential targets for reversing cisplatin resistance.