MIR-34B-3P ENHANCES CHEMOSENSITIVITY TO CISPLATIN IN A549/DDP CELLS IN VITRO BY P53 PATHWAY

Tinghua Zhang^{1, 2, *}, Youyuan Hu³

¹Clinical Laboratory, The Second People’s Hospital of Huaihua City, Huaihua, Hunan, China - ²Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China - ³Pathology Laboratory, The Second People’s Hospital of Huaihua City, Huaihua, Hunan, China

Background: MicroRNAs play an important role in cisplatin resistance, but there are very few studies on miR-34b-3p. Therefore, further testing is needed to investigate the regulatory role of miR-34b-3p in A549/DDP cells and its 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 and A549/DDP cells was detected by real-time PCR. A549/DDP cells were transfected with miR-34b-3p mimic for overexpression. CCK-8, flow cytometry, scratch assay, and western blot assay were used to detect changes in cells after transfection.

Results: MiR-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 proliferation and migration, arrest cell cycle progression, promote cell apoptosis, and increase the expression of p21 and Bax in the p53 signaling pathway.

Conclusions: MiR-34b-3p enhances chemosensitivity to cisplatin in A549/DDP cells in vitro. The results suggest that miR-34b-3p could become a potential biomarker and a new therapeutic target for chemoresistance reversal in the future.