顺铂类化疗已被广泛应用于肺腺癌（LUAD）的治疗。然而，顺铂耐药的发展成为影响治疗效果的重要障碍。了解顺铂耐药的分子机制仍然是必要的。根据CCLE数据库，将肺癌细胞系分为顺铂耐药组和顺铂敏感组。筛选出差异表达的miRNA，并进行生存预后分析进行进一步鉴定。通过转染miR-375抑制子或模拟子，在细胞毒性实验、流式细胞术和Western印迹中验证miR-375的作用。根据TransmiR构建转录因子（TF）-miRNA网络。通过Starbase预测miR-375的靶基因，并通过Human Protein Atlas的RT-qPCR和免疫组化结果进行进一步验证。使用GO术语和KEGG进行功能富集分析。 本研究发现miR-375具有促进LUAD的顺铂敏感性和凋亡的能力。分析了与miR-375在LUAD中相关的基因，ABCC8显示最强的正相关性。此外，预测了调节miR-375表达的转录因子。MBNL1、PTPN3、PRKD1和RPN1被确定为miR-375的靶基因。富集分析表明，与miR-375相关的基因与促进细胞增殖和抑制凋亡有关，涉及MAPK信号通路。 总的来说，本研究为miR-375在LUAD的顺铂敏感性方面提供了新的见解。我们的研究结果可能成为顺铂耐药的新治疗策略和预测模型的理论基础。 版权所有 © 2023 Elsevier GmbH出版。

Cisplatin-based chemotherapy has been widely used in the treatment of lung adenocarcinoma (LUAD). However, the development of cisplatin resistance becomes a major obstacle impeding the curative effect. It remains necessary to uncover the molecular mechanism of cisplatin resistance.Based on the CCLE database, lung cancer cell lines were divided into cisplatin-resistant and cisplatin-sensitive groups. The differentially expressed miRNAs were filtered and further identified by survival prognosis analysis. After transfection with miR-375 inhibitor or mimic, cell cytotoxicity assay, flow cytometry and western blot were conducted to validate the role of miR-375. The transcription factor (TF)-miRNA network was constructed based on TransmiR. The target genes of miR-375 were predicted by Starbase and further verified by RT-qPCR and immunohistochemistry results in the Human Protein Atlas. Functional enrichment analysis was performed with GO terms and KEGG.In this study, miR-375 showed the ability to promote cisplatin sensitivity and apoptosis of LUAD. Genes correlated with miR-375 in LUAD were analyzed and ABCC8 showed the strongest positive correlation. Moreover, transcription factors that regulate miR-375 expression were predicted. MBNL1, PTPN3, PRKD1 and RPN1 were identified as the target genes of miR-375. Enrichment analysis demonstrated that miR-375-related genes associated with promoting cell proliferation and anti-apoptosis were involved in the MAPK signaling pathway.Overall, this study provides new insights into the role of miR-375 in the cisplatin sensitivity of LUAD. Our present findings may serve as a theoretical basis for new therapeutic strategies and predictive models of cisplatin resistance in LUAD.Copyright © 2023. Published by Elsevier GmbH.