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miR-140-3p attenuated the tumorigenesis of multiple myeloma via attenuating BZW2
Xingxing Long1, Junjun Li1, Feng Wen1
1Department of Hematology, The 1st Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, People's Republic of China.
Background:
Among B-cell lymphoma, multiple myeloma (MM) is an incurable malignancy. miR-140-3p was known to be an inhibitor in malignant tumors. However, the function of miR-140-3p in MM remains unclear.
Methods:
qRT-PCR was performed to determine the expressions of miR-140-3p and BZW2 mRNA. The protein level of BZW2 was determined by the western blot. Cell viability or cell apoptosis was detected by the MTT assay or flow cytometry, respectively. Binding between miR-140-3p and BZW2 was validated using the dual luciferase assay. Xenograft model was applied to verify the results of in vitro study.
Results:
The level of miR-140-3p was significantly downregulated in MM. Overpexression of miR-140-3p impaired the proliferation of MM cell lines and induced apoptosis in MM cells. miR-140-3p was validated to target BZW2 and inhibit the expression of BZW2. BZW2 was involved in the regulation of miR-140-3p on MM cell vitality and apoptosis. In vivo study revealed that miR-140-3p impeded tumorigenesis of MM cell line in nude mice.
Conclusion:
Our present study revealed that miR-140-3p served as a suppressor in MM by negatively regulating BZW2. Thus, miR-140-3p could act as a new target for treating MM.
Insights
MicroRNA-140-3p suppresses multiple myeloma (MM) by targeting BZW2. This study identifies miR-140-3p as a potential therapeutic target for treating this incurable B-cell malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) is an incurable B-cell malignancy.
- The role of microRNA-140-3p (miR-140-3p) in MM pathogenesis is not well understood.
- Previous studies suggest miR-140-3p acts as a tumor suppressor in other cancers.
Purpose of the Study:
- To investigate the function of miR-140-3p in multiple myeloma.
- To identify the molecular targets of miR-140-3p in MM.
- To evaluate the therapeutic potential of miR-140-3p in MM.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure miR-140-3p and BZW2 mRNA expression.
- Western blot analysis for BZW2 protein levels.
- Cell viability (MTT assay) and apoptosis assays (flow cytometry).
- Dual luciferase reporter assay to confirm direct targeting.
- Xenograft mouse model for in vivo validation.
Main Results:
- miR-140-3p expression was significantly downregulated in MM.
- Overexpression of miR-140-3p inhibited MM cell proliferation and induced apoptosis.
- miR-140-3p directly targets BZW2, suppressing its expression.
- BZW2 mediates the effects of miR-140-3p on MM cell viability and apoptosis.
- In vivo studies demonstrated that miR-140-3p impedes MM tumor growth.
Conclusions:
- miR-140-3p functions as a tumor suppressor in multiple myeloma.
- The suppressive role of miR-140-3p in MM is mediated through the negative regulation of BZW2.
- miR-140-3p represents a promising novel therapeutic target for MM treatment.
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