Abstract
OBJECTIVE: To explore the impact of low miR-369-3p expression on the resistance of PC-9 cells to osimertinib. METHODS: The PC-9/AZD9291 cell line was established with osimertinib. Real-time quantitative PCR was employed to measure the expression levels of miR-369-3p in both PC-9 and PC-9/AZD9291 cells, and Western blotting was utilized to detect PTPN12 protein expression. A dual-luciferase reporter assay was conducted to investigate the target relationship between miR-369-3p and PTPN12. CCK8 assays were performed to evaluate the impact of miR-369-3p inhibition on drug resistance. RESULTS: In comparison to PC-9 cells, there was a significant upregulation of miR-369-3p and downregulation of PTPN12 protein in PC-9/AZD9291 cells (p < 0.05). Transfection with the miR-369-3p inhibitor resulted in decreased levels of miR-369-3p and increased expression of PTPN12 protein in PC-9/AZD9291 cells (p < 0.05). Conversely, transfection with miR-369 mimics led to an increase in miR-369-3p levels accompanied by a decrease in PTPN12 protein (p < 0.05). Notably, treatment with the miR-369-3p inhibitor lowered the IC50 value for PC-9/AZD9291 cells; however, following downregulation of PTPN12 using PTPN12-siRNA, sensitivity due to low expression of miR-369-3p was significantly diminished (p < 0.05). CONCLUSION: miR-369-3p plays a crucial role in modulating drug resistance in PC-9/AZD9291 cells against osimertinib through regulation of PTPN12.