MiR-375 promotes cisplatin sensitivity of lung adenocarcinoma

作者：Du, Shuomeng; Qu, Han; Zhang, Ying; Zhu, Shihao; Wang, Yang; Zhang, Shuopeng; Wang, Zhao; Yang, Qian; Fu, Songbin; Dong, Kexian^*

来源：Pathology Research and Practice, 2023, 249: 154765.

DOI：10.1016/j.prp.2023.154765

• Lung adenocarcinoma
• Cisplatin
• MiR-375
• Drug sensitivity
• MAPK pathway

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.

• 单位
  哈尔滨医科大学