MiR-34b-3p Enhances Chemosensitivity To Cisplatin In Non-small Cell Lung Cancer And Its Mechanism

Objective:To investigate the regulatory role of miR-34b-3p in cisplatin resistance in non-small cell lung cancer and its molecular mechanism.Methods:Differentially expressed miRNAs were screened in both TCGA and GEO databases by bioinformatic analysis,and the target miRNA was selected as miR-34b-3p.The expression of miR-34b-3p in A549 cells（lung adenocarcinoma cells）and A549/DDP cells（cisplatin-resistant lung adenocarcinoma cells）was detected by real-time PCR.A549/DDP cells were transfected with miR-34b-3p mimic for overexpression.CCK-8,flow cytometry,Hoechst 33258 stain,scratch assay and western blot assay were used to detect IC₅₀ of transfected cells to cisplatin,cell proliferation,cell cycle,cell apoptosis,cell migration and changes in p53 signaling pathway.Results:Mi R-34b-3p was downregulated in lung cancer and was significantly differentially expressed in cisplatin-resistant samples according to bioinformatic analysis.The expression of miR-34b-3p was significantly downregulated in A549/DDP cells by real-time PCR.A549/DDP transfected with miR-34b-3p mimic became sensitive to cisplatin and the IC₅₀ decreased significantly.Overexpression of miR-34b-3p can inhibit the proliferation and migration,arrest cell cycle progression,promote cell apoptosis,and increase the expression of p21and Bax in the p53 signaling pathway.Conclusion:Overexpression of miR-34b-3p may increase the sensitivity of A549/DDP cells to cisplatin by inhibiting cell proliferation and migration,arresting the cell cycle,and promoting apoptosis.The underlying mechanism could be related to the increased expression of p21and Bax by miR-34b-3p.The results suggest that miR-34b-3p could become a potential biomarker and a new therapeutic target for chemoresistance reversal.