期刊
PATHOLOGY RESEARCH AND PRACTICE
卷 249, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.prp.2023.154765
关键词
Lung adenocarcinoma; Cisplatin; MiR-375; Drug sensitivity; MAPK pathway
类别
This study reveals the role of miR-375 in cisplatin sensitivity of LUAD, showing its ability to promote apoptosis and sensitivity to cisplatin. The analysis of miR-375-related genes and its involvement in the MAPK signaling pathway provide new insights into potential therapeutic strategies and predictive models for cisplatin resistance in LUAD.
Background: 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.Methods: Based on the CCLE database, lung cancer cell lines were divided into cisplatin-resistant and cisplatinsensitive 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.Results: 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.Conclusion: 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.
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