Metformin alleviates breast cancer through targeting high-mobility group AT-hook 2
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Published on: June 9, 2023
1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China.
Background:
As a classic oral drug used in diabetic patients, metformin has exhibited an anticancer role in many types of cancers in recent years. Here, we aimed to investigate the role of metformin in the growth of breast cancer and its novel targets.
Methods:
A cell viability assay was utilized to examine the inhibitory effect of metformin on proliferation of breast cancer cells. Western blotting and RT-PCR assays were used to detect the regulation of metformin on the expression of oncogenic HMGA2. The luciferase reporter vector of HMGA2 promoter was constructed. A luciferase reporter gene assay was performed to analyze the effect of metformin on HMGA2 promoter activity in breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was performed to show the binding of Sp1 to HMGA2 promoter in breast cancer cells with or without metformin treatment. The function of metformin-regulated HMGA2 in breast cancer growth was tested using a cell viability assay.
Results:
Cell proliferation was obviously inhibited in breast cancer cells treated with different concentrations of metformin. The level of mRNA and protein of HMGA2 was significantly reduced by metformin in the cells. Mechanistically, metformin was able to inactivate the HMGA2 promoter through downregulating transcription factor Sp1 in the cells. In terms of function, treatment with metformin suppressed the proliferation of breast cancer cells and overexpressed HMGA2 reversed the inhibition of cell proliferation mediated by metformin.
Conclusion:
Metformin resists the growth of breast cancer through targeting Sp1/HMGA2 signal.
Insights
Metformin, an oral diabetes drug, inhibits breast cancer growth by targeting the Sp1/HMGA2 pathway. This study reveals metformin
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Metformin, a common oral medication for diabetes, has demonstrated potential anticancer properties across various cancer types.
- Emerging research suggests metformin may play a role in breast cancer progression and presents an opportunity to identify novel therapeutic targets.
Purpose of the Study:
- To investigate the specific effects of metformin on breast cancer cell growth.
- To identify and elucidate the molecular targets through which metformin exerts its anticancer effects in breast cancer.
Main Methods:
- Cell viability assays were employed to assess metformin's impact on breast cancer cell proliferation.
- Western blotting and RT-PCR were used to analyze metformin's regulation of HMGA2 expression.
- Luciferase reporter assays and Chromatin Immunoprecipitation (ChIP) were utilized to explore the mechanism involving Sp1 and HMGA2 promoter activity.
Main Results:
- Metformin significantly inhibited breast cancer cell proliferation in a dose-dependent manner.
- Metformin treatment led to a notable reduction in both mRNA and protein levels of HMGA2.
- The drug suppressed HMGA2 promoter activity by downregulating the transcription factor Sp1, and HMGA2 overexpression counteracted metformin's inhibitory effects.
Conclusions:
- Metformin effectively inhibits breast cancer growth.
- The anticancer effect of metformin is mediated through the Sp1/HMGA2 signaling pathway.
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