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MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells.
- Source :
-
Cell cycle (Georgetown, Tex.) [Cell Cycle] 2023 Jun; Vol. 22 (11), pp. 1367-1379. Date of Electronic Publication: 2023 Apr 28. - Publication Year :
- 2023
-
Abstract
- The main objective of this study is to investigate the regulatory roles of the miR-17-5p/RRM2 axis in A549/G+ cells' gemcitabine resistance. The cell viability was determined using CCK8 and clonogenic assays. Gene expression level analysis by RT-qPCR and Western blotting. Cell cycle analysis by flow cytometry. The dual luciferase activity assay was used to verify the target gene of miR-17-5p. In gemcitabine-resistant cell line A549G+, the drug resistance decreased after up-regulation of MiR-17-5p expression. The proportion of cell cycle G1 phase increased, and the S phase decreased. The expression level of cell cycle-related proteins CCNE1, CCNA2, and P21 decreased. The opposite results emerged after the down-regulation of MiR-17-5p expression in gemcitabine-sensitive cell line A549G-. The expression levels of PTEN and PIK3 in A549G+ cells were higher than in A549G-cells, but p-PTEN was lower than that in A549G-. After up-regulating the expression of MiR-17-5p in A549G+, the expression levels of p-PTEN increased, and the expression level of p-AKT decreased. After down-regulating miR-17-5p expression, the opposite results emerged. The dual-luciferase reporter assay and restorative experiments proved that RRM2 is one of the target genes for MiR-17-5p. Our results suggested that the miR-17-5p/RRM2 axis could adjust gemcitabine resistance in A549 cells, and the p-PTEN/PI3K/AKT signal pathway might be involved in this regulatory mechanism.
Details
- Language :
- English
- ISSN :
- 1551-4005
- Volume :
- 22
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cell cycle (Georgetown, Tex.)
- Publication Type :
- Academic Journal
- Accession number :
- 37115505
- Full Text :
- https://doi.org/10.1080/15384101.2023.2207247