MiR-124-3p Enhances the Sansitivity of Chronic Myelogenous Leukemia Cell K562-R to Imatinib by Targeting ABCA2.
10.19746/j.cnki.issn.1009-2137.2020.03.012
- Author:
Feng-Juan ZHANG
1
;
Wei-Jie CAO
2
;
Fang-Fang CHANG
1
;
Fu-Yun HUANG
1
;
Jian-Xin GUO
3
,
4
Author Information
1. Department of Internal Medicine Teaching and Research Section of Henan Medical College, Zhengzhou 451191, Henan Province, China.
2. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
3. Department of Internal Medicine Teaching and Research Section of Henan Medical College, Zhengzhou 451191, Henan Province, China,E-mail: guojianxin888@
4. com.
- Publication Type:Journal Article
- MeSH:
ATP-Binding Cassette Transporters;
Animals;
Apoptosis;
Cell Proliferation;
Humans;
Imatinib Mesylate;
K562 Cells;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
Mice;
Mice, Nude;
MicroRNAs
- From:
Journal of Experimental Hematology
2020;28(3):789-796
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect and mechanism of miR-124-3p-targeing regulating ABCA2 on chronic myelogenous leukemia cell K562-R.
METHODS:CML cells with miR-124-3p-overexpression and ABCA2-over-expression as well as subcutaneoustrans planted tumor nude mice were used as study objects. And the CML cells were divided into four groups: K562-R blank control, miR-124-3p mimic control, ABCA2-overexpression and mimic+PC ABCA2. The effects of miR-124-3p and ABCA2 on CML cells were analyzed. The levels of proliferation-, apoptosis- and autophagy- related protein were determined by Western blot. qRT-PCR was employed to detect the levels of miR-124-3p and ABCA2 in K562-R cells. The relationship between miR-124-3p and ABCA2 was validated by luciferase reporter system assays and bioinformatics. Hoechst/immunohistochemical staining and CCK-8 assay were performed to investigate the function involved.
RESULTS:miR-124-3p highly expressed in K562-S cells and lowly expressed in K562-R cells, however, ABCA2 lowly expressed in K562-S cells and highly expressed in K562-R cells. Over-expression of miR-124-3p significantly decreased ABCA2 level and cell growth, but increased autophagy and apoptosis in K562-R cells (P＜0.01). When ABCA2 was over-expressed, the K562-R cell growth was promoted and autophagy and apoptosis were inhibited (P＜0.01). The miR-124-3p promoted cell autophagy and apoptosis but inhibited cell growth in nude mice transplant tumor model (P＜0.01).
CONCLUSION:miR-124-3p can target ABCA2 to inhibit the growth of CML cells and promote the cell autophagy and apoptosis of CML cells.
