MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells

Ma，Xuan1; Fu，Tian2; Ke，Zhi Yin3; Du，Shen Lin4; Wang，Xue Chun3; Zhou，Ning5; Zhong，Mu Yi6; Liu，Yong Jun3; Liang，Ai Ling3

2023

10.1080/15384101.2023.2207247

Cell Cycle   影响因子和分区

1538-4101

1551-4005

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.

Gemcitabine MiR-17-5p RRM2

SCI

英语

其他

National Natural Science Foundation of China[81071853]

Cell Biology

Cell Biology

WOS:000979091100001

TAYLOR & FRANCIS INC

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85158898590

Scopus

1.Department of Biochemistry and Molecular Biology & Department of Clinical Biochemistry,Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics,Guangdong Medical University,Dongguan,China
2.Department of Clinical Laboratory,Xinle City Hospital,Shijiazhuang,China
3.Department of laboratory,Zhanjiang Central Hospital,Zhanjiang,Guangdong,China
4.Department of clinical laboratory,Dongguan People’s Hospital,Dongguan,China
5.Department of Clinical Laboratory,Southern University of Science and Technology Hospital,Shenzhen,China
6.Department of breast,Dongguan People’s Hospital,Dongguan,China

Ma，Xuan,Fu，Tian,Ke，Zhi Yin,et al. MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells[J]. Cell Cycle,2023,22(11).

Ma，Xuan.,Fu，Tian.,Ke，Zhi Yin.,Du，Shen Lin.,Wang，Xue Chun.,...&Liang，Ai Ling.(2023).MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells.Cell Cycle,22(11).

Ma，Xuan,et al."MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells".Cell Cycle 22.11(2023).