2. Academic Validation
  3. MiR-375 promotes cisplatin sensitivity of lung adenocarcinoma

MiR-375 promotes cisplatin sensitivity of lung adenocarcinoma

  • Pathol Res Pract. 2023 Sep:249:154765. doi: 10.1016/j.prp.2023.154765.
Shuomeng Du 1,  Han Qu 1,  Ying Zhang 1,  Shihao Zhu 1,  Yang Wang 1,  Shuopeng Zhang 1,  Zhao Wang 2,  Qian Yang 1,  Songbin Fu 1,  Kexian Dong 3
Affiliations

Affiliations

  • 1 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China.
  • 2 Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China.
  • 3 Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China; Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China. Electronic address: [email protected].
PMID: 37625279 DOI: 10.1016/j.prp.2023.154765
Abstract

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 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.

Keywords

Cisplatin; Drug sensitivity; Lung adenocarcinoma; MAPK pathway; MiR-375.

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