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微小RNA-369-3p通过靶向蛋白酪氨酸磷酸酶非受体型12来调节肺癌细胞的耐药性。

miR-369-3p regulates the drug resistance of lung cancer cells by targeting PTPN12.

作者信息

Wang Yan, Wang XiaoLi, Xu Jun, Zhang Didi, Cao YongFeng

机构信息

Department of Medical Oncology, Tumor Hospital Affiliated to Nantong University & Nantong Tumor Hospital, Nantong, Jiangsu, China.

出版信息

Pharmacogenomics. 2025 Apr-Apr;26(5-6):165-170. doi: 10.1080/14622416.2025.2504864. Epub 2025 May 14.

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 ( < 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 ( < 0.05). Conversely, transfection with miR-369 mimics led to an increase in miR-369-3p levels accompanied by a decrease in PTPN12 protein ( < 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 ( < 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.

摘要

目的

探讨低表达的miR-369-3p对PC-9细胞对奥希替尼耐药性的影响。

方法

用奥希替尼建立PC-9/AZD9291细胞系。采用实时定量PCR检测PC-9和PC-9/AZD9291细胞中miR-369-3p的表达水平,并用蛋白质免疫印迹法检测PTPN12蛋白表达。进行双荧光素酶报告基因检测以研究miR-369-3p与PTPN12之间的靶向关系。采用CCK8法评估抑制miR-369-3p对耐药性的影响。

结果

与PC-9细胞相比,PC-9/AZD9291细胞中miR-369-3p显著上调,PTPN12蛋白下调(<0.05)。用miR-369-3p抑制剂转染导致PC-9/AZD9291细胞中miR-369-3p水平降低,PTPN12蛋白表达增加(<0.05)。相反,用miR-369模拟物转染导致miR-369-3p水平升高,同时PTPN12蛋白减少(<0.05)。值得注意的是,用miR-369-3p抑制剂处理降低了PC-9/AZD9291细胞的IC50值;然而,使用PTPN12-siRNA下调PTPN12后,由于miR-369-3p低表达导致的敏感性显著降低(<0.05)。

结论

miR-369-3p通过调节PTPN12在调节PC-9/AZD9291细胞对奥希替尼的耐药性中起关键作用。

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