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Effect and Mechanism of Curcumin on EZH2 - miR-101 Regulatory Feedback Loop in Multiple Myeloma
Chuanqing Wu1, Tuo Ruan1, Weizhen Liu1
1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.
Background:
Multiple myeloma is the second most prevalent hematologic malignancy and thought to be incurable. Therefore, it's urgent to find new drugs for treatment. Some experiments have shown that curcumin might have great potential in treating multiple myeloma, while the mechanism is still unknown. EZH2 and SUZ12 are the core proteins in PRC2 and their expressions are increased in various human cancers, including the poor prognostic multiple myeloma. Meanwhile, the regulation of miRNAs and EZH2 has been demonstrated in other cancer researches, like lung cancer, pancreatic cancer, leukemia and so on.
Objective:
To reveal the mechanism behind the anti-tumor effect of cucurmin in multiple myeloma.
Method:
The effect of curcumin on the growth of MM cells was studied by MTT assay in the MM cell lines RPMI8226 and U266. Apoptosis was measured by Annexin V-FITC/PI double staining method. Western blotting, RT-PCR and luciferase activity assay were used to assess the expression of EZH2, SUZ12, miR-101 and downstream proteins such as E-cadherin, MMP9, c-Myc, cyclin D3, CDK4 and CDK6.
Results:
Curcumin could significantly inhibite the proliferation of MM cells in a time- and concentrationdependent manner. Curcumin induced apoptosis by inhibiting the expression of EZH2, and the apoptosis rates were 16.42% and 25.62% when the RPMI8226 cells incubated with 5 and 10 µmol/L of curcumin. For U266 cells, the apoptosis rates were 15.25% and 21.28%. The up-regulation of miR-101 led to the lower expression of EZH2. In adverse, the expression of EZH2 induced lower expression of miR-101. The down-stream proteins of miR-101 were regulated by curcumin and EZH2 at the same time.
Conclusion:
Our experiments verified that the effect and mechanism of curcumin on multiple myeloma is via EZH2 - miR-101 regulatory feedback loop, which would lead us to a new way of investigating multiple myeloma and come up with new therapies in treating the disease.
Insights
Curcumin inhibits multiple myeloma cell growth by targeting the EZH2-miR-101 feedback loop. This research uncovers a novel therapeutic mechanism for this incurable hematologic malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multiple myeloma (MM) is a prevalent, incurable hematologic malignancy.
- Curcumin shows potential for MM treatment, but its mechanism is unclear.
- EZH2 and SUZ12 proteins are upregulated in MM and other cancers.
Purpose of the Study:
- To elucidate the anti-tumor mechanism of curcumin in multiple myeloma.
- To investigate the role of EZH2 and miR-101 in curcumin's effects on MM cells.
Main Methods:
- MTT assays for cell proliferation, Annexin V/PI for apoptosis.
- Western blotting, RT-PCR, and luciferase assays for gene and protein expression.
- Assessed EZH2, SUZ12, miR-101, and downstream target protein levels.
Main Results:
- Curcumin inhibited MM cell proliferation and induced apoptosis in a dose-dependent manner.
- Curcumin treatment led to decreased EZH2 expression and increased miR-101 levels.
- A feedback loop between EZH2 and miR-101 was identified, regulating downstream proteins.
Conclusions:
- Curcumin exerts anti-myeloma effects through the EZH2-miR-101 regulatory feedback loop.
- This mechanism offers a new therapeutic strategy for multiple myeloma.
- Further research into this pathway may yield novel treatments for MM.
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