MiR-375 promotes cisplatin sensitivity of lung adenocarcinoma

作者：Shuomeng Du, Han Qu, Ying Zhang, Shihao Zhu, Yang Wang, Shuopeng Zhang, Zhao Wang, Qian Yang, Songbin Fu, Kexian Dong · 发表于：Pathology - Research and Practice · 年份：2023 · DOI：10.1016/j.prp.2023.154765 · 被引用次数：8 · 研究领域：MicroRNA in disease regulation、Lung Cancer Treatments and Mutations、Circular RNAs in diseases

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 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. 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 MA...