Abstract: Objective To investigate the role of miR⁃130a⁃3p in cisplatin⁃resistant  small cell lung cancer (SCLC) and explore its underlying molecular mechanisms. Methods Cisplatin⁃resistant SCLC cell line (H446/EP) was established using a concentration⁃gradient induction method. The SCLC cells were transfected with miR⁃130a⁃3p mimics via lipofection. Cell proliferation viability was assessed using the CCK⁃8 assay, while apoptosis rates and cell cycle distribution were analyzed by flow cytometry. Bioinformatics analysis was performed using TargetScan, TarBase, and miRWalk databases to predict the targeting relationship between miR⁃130a⁃3p and ATG2B. The expression levels of miR⁃130a⁃3p and ATG2B mRNA were detected by quantitative real⁃time PCR (qRT⁃PCR). Protein expression of autophagy⁃related proteins, including ATG2B, LC3B, p62, and Beclin1 were measured by Western blot. The fluorescence intensity of LC3B and p62 proteins was quantified by immunofluorescence to evaluate cellular autophagy activity. Results The resistance index of H446/EP cells was 6.465, with miR⁃130a⁃3p expression was significantly lower than in the sensitive parent cells. Restoring miR⁃130a⁃3p expression effectively inhibited proliferation and promoted apoptosis in the resistant cells (all P<0.05). Bioinformatics prediction indicated that ATG2B is a high⁃confidence target gene of miR⁃130a⁃3p. Overexpression of with miR⁃130a⁃3p suppressed the expression of the autophagy⁃related gene ATG2B, leading to decreased LC3B⁃Ⅱ/LC3B⁃Ⅰ ratio and Beclin1 levels (all P<0.05), while upregulating p62 levels (P<0.05). Conclusions miR⁃130a⁃3p mediates cisplatin resistance in SCLC cells through regulating ATG2B expression. Enhancing miR⁃130a expression may provide a novel strategy for overcoming platinum resistance in SCLC.

Key words: Small cell lung cancer, miR?130a?3p, ATG2B, Cisplatin； Resistance