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Published on: October 23, 2019
[MiR-124-3p Enhances the Sansitivity of Chronic Myelogenous Leukemia Cell K562-R to Imatinib by Targeting ABCA2]
Feng-Juan Zhang1, Wei-Jie Cao2, Fang-Fang Chang1
1Department of Internal Medicine Teaching and Research Section of Henan Medical College, Zhengzhou 451191, Henan Province, China.
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.
Insights
MicroRNA-124-3p targets ABCA2 to inhibit chronic myelogenous leukemia (CML) cell growth. This microRNA promotes CML cell autophagy and apoptosis, offering a potential therapeutic strategy for CML.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome.
- Drug resistance in CML, particularly in K562-R cells, remains a significant clinical challenge.
- MicroRNAs (miRNAs) play crucial roles in regulating gene expression and are implicated in various cancers, including CML.
Purpose of the Study:
- To elucidate the role of miR-124-3p in regulating ABCA2 expression in K562-R CML cells.
- To investigate the mechanistic link between miR-124-3p, ABCA2, and the biological behavior of CML cells.
- To assess the therapeutic potential of modulating miR-124-3p in a CML model.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-124-3p and ABCA2 levels.
- Western blot analysis to assess protein expression related to proliferation, apoptosis, and autophagy.
- Luciferase reporter assays and bioinformatics to confirm the interaction between miR-124-3p and ABCA2.
- Cell viability assays (CCK-8) and in vivo studies using subcutaneous tumor xenografts in nude mice.
Main Results:
- miR-124-3p was downregulated, while ABCA2 was upregulated in K562-R CML cells compared to K562-S cells.
- Overexpression of miR-124-3p significantly reduced ABCA2 levels, inhibited K562-R cell proliferation, and enhanced autophagy and apoptosis.
- Conversely, ABCA2 overexpression promoted K562-R cell growth and suppressed autophagy and apoptosis.
- In vivo studies confirmed that miR-124-3p overexpression inhibited tumor growth and promoted apoptosis in nude mice.
Conclusions:
- miR-124-3p functions as a tumor suppressor in CML by targeting ABCA2.
- Modulating miR-124-3p can inhibit CML cell proliferation and induce apoptosis and autophagy.
- The miR-124-3p/ABCA2 axis represents a potential therapeutic target for overcoming drug resistance in CML.
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