MicroRNA-150-3p enhances the antitumour effects of CGP57380 and is associated with a favourable prognosis in non-small cell lung cancer

Sci Rep. 2025 Jan 15;15(1):1973. doi: 10.1038/s41598-025-85793-7.

Abstract

MicroRNA (miRNA) dysregulation has been identified in several carcinomas, including non-small cell lung cancer (NSCLC), and is known to play a role in the development and progression of this disease. We initially conducted a miRNA microarray analysis, which revealed that the MNK inhibitor CGP57380 increased the expression of miR-150-3p. A similar analysis was performed using data from The Cancer Genome Atlas (TCGA). Cell proliferation, colony formation and migration assays were validated in A549 and H157 cells treated with miR-150-3p mimics. Quantitative polymerase chain reaction (qPCR) was then used to detect potential target genes. We observed significant downregulation of miR-150-3p in NSCLC samples compared with normal samples (P = 0.035). High miR-150-3p expression was associated with longer overall survival (P = 0.005), as determined via a tissue microarray (TMA). These results were validated in the TCGA and revealed that miR-150-3p was expressed at low levels in NSCLC tissues (P < 0.0001) and that patients with high miR-150-3p expression had a better prognosis (P = 0.042). Moreover, the combination of miR-150-3p and CGP57380 exerted a synergistic inhibitory effect on colony formation, growth, and migration and induced apoptosis in NSCLC cell lines. We investigated the potential targets of miR-150-3p and successfully validated six potential target genes through qPCR analysis. High miR-150-3p expression may enhance the response to immunotherapy, cisplatin and gemcitabine. In summary, this study underscores the promising therapeutic implications of combining miR-150-3p and CGP57380 for NSCLC treatment. Additionally, this study provides valuable insights into the molecular mechanisms underlying the effects of this treatment.

Keywords: MNK inhibitor; MicroRNA; Non-small cell lung cancer; Targeted therapy.

MeSH terms

  • A549 Cells
  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation* / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Prognosis

Substances

  • MicroRNAs
  • MIRN150 microRNA, human
  • Antineoplastic Agents
  • Deoxycytidine