MiR-133a-3p overexpression-induced elevation of cisplatin-mediated chemosensitivity to non-small cell lung cancer by targeting replication factor C3

Investigated the role of miR-133a-3p expression in NSCLC resistance to cisplatin (DDP) treatment and elucidate the possible mechanisms. MiR-133a-3p expression levels in DDP-resistant cells (SPC-1/DPP and A549/DDP) were measured using quantitative reverse-transcription polymerase chain reaction. Cell proliferation, cell apoptosis, cell cycle distribution, and DDP sensitivity were detected through flow cytometry, Cell Counting Kit-8 (CCK-8) and western blot analysis. In addition, databases were used to predict the miR-133a-3p targets, confirmed by dual-luciferase reporter assay. The miR-133a-3p expression levels obviously decreased in the A549/DDP and SPC-1/DPP cells [**P < 0.01; (n = 3)]. Upregulation of the miR-133a-3p expression notably suppressed cell growth, enhanced cell apoptosis, and resulted in cell cycle arrest in the SPC-1/DPP and A549/DDP cells. CCK-8 assay for the detection of proliferation of the miR-133a-3p mimic-transfected A549/DDP and SPC-A1/DDP cells treated with different DDP doses revealed IC50 values of NC mimic group: 6.85 mu g/mL; miR-133a-3p mimic: 3.9 mu g/mL and NC mimic group: 6.9 mu g/mL; miR-133a-3p mimic: 3.99 mu g/mL, respectively]. By contrast, it elevated DDP sensitivity in the A549/DDP cells and DDP resistance in the SPC-1/DPP cells. Mechanically, miR-133a-3p negatively regulated replication factor C3 and promoted DDP sensitivity in the SPC-1/DPP and A549/DDP cells, 94 potential targets that might bind to miR-133a-3p were identified.

Automated summary

The study focused on the role of miR-133a-3p in cisplatin resistance in non-small cell lung cancer. Upregulation of miR-133a-3p led to inhibited cell growth and enhanced apoptosis, while lowering resistance to cisplatin. The mechanism involved negative regulation of replication factor C3 and identification of 94 potential target genes for miR-133a-3p.