The Role and Mechanism of MiR-451 in Multidrug Resistance of Leukemia Cell Line K562/A02.
10.19746/j.cnki.issn.1009-2137.2023.03.011
- Author:
Yan-Li FENG
1
;
Bao-Xiong SU
1
;
Fan-Mei GE
1
;
Chong-Wen DAI
2
Author Information
1. Department of Hematology, Yan'an University Affiliated Hospital, Yan'an 716000, Shaanxi Province, China.
2. Department of Hematology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.E-mail: daicw@sina.com.
- Publication Type:Journal Article
- Keywords:
leukemia;
miR-451;
multidrug resistance
- MeSH:
Humans;
K562 Cells;
Drug Resistance, Neoplasm/genetics*;
Drug Resistance, Multiple/genetics*;
Doxorubicin/pharmacology*;
MicroRNAs/genetics*;
Leukemia/genetics*;
RNA, Messenger
- From:
Journal of Experimental Hematology
2023;31(3):685-692
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To detect the differential expressions of miR-451, ABCB1 and ABCC2 in drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, and explore the regulatory relationship between miR-451 and the expressions of ABCB1 and ABCC2 , and the mechanism of miR-451 involved in drug resistance in leukemia.
METHODS:CCK-8 assay was used to detect the drug resistance of K562/A02 and K562 cells. Quantitative Real-time PCR (qRT-PCR) was used to verify the differential expressions of miR-451 in K562 and K562/A02 cells. MiR-451 mimic and negative control (miR-NC), miR-451 inhibitor and negative control (miR-inNC) were transfected into K562 and K562/A02 cells respectively, then qRT-PCR and Western blot were used to detect the expression levels of mRNA and protein of ABCB1 and ABCC2 in K562 and K562/A02 cells and the transfected groups.
RESULTS:The drug resistance of K562/A02 cells to adriamycin was 177 times higher than that of its parent cell line K562. Compared with K562 cells, the expression of miR-451 in K562/A02 cells was significantly higher (P <0.001), and the mRNA and protein expression levels of ABCB1 and ABCC2 in K562/A02 cells were significantly higher than those in K562 cells (P <0.001). After transfected with miR-451 inhibitor, the expression of miR-451 was significantly down-regulated in K562/A02 cells (P <0.001), the sensitivity to chemotherapy drugs was significantly enhanced (P <0.05), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly decreased (P <0.01). After transfected with miR-451 mimic, the expression of miR-451 was significantly upregulated in K562 cells (P <0.001), and the mRNA and protein expressions of ABCB1 and ABCC2 were significantly increased (P <0.01).
CONCLUSION:There are significant differences in the expressions of miR-451, ABCB1 and ABCC2 between the drug-sensitive leukemia cell line K562 and drug-resistant cell line K562/A02, which suggests that miR-451 may affect the drug resistance of leukemia cells by regulating the expression of ABCB1 and ABCC2.
