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Published on: February 9, 2024
MAFIP is a tumor suppressor in cervical cancer that inhibits activation of the nuclear factor-kappa B pathway
1State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
Abstract:
Cervical cancer is the second most common cancer in women. Inactivation of tumor suppressor genes underlies the transformation and progression of cervical cancer. Previously, we reported MAFIP can inhibit the growth of human cervical cancer HeLa cells. In this study, MAFIP was found to be downregulated in cervical intraepithelial neoplasia tissues. Induced expression of MAFIP in HeLa cells strongly inhibited tumor formation in nude mice, confirming its tumor suppressor activity in vivo. Overexpression of MAFIP inhibited activation of the NF-κB pathway, a commonly active pathway in cancer cells, by preventing the phosphorylation of IKK and IκBα, degradation of IκBα and the nuclear localization of p65. Induction of c-myc, an oncogene controlled by NF-κB, was severely impaired in the cells overexpressing MAFIP. In contrast, knockdown of MAFIP by siRNA activated the NF-κB pathway and promoted cell proliferation. These data suggest MAFIP functions as a tumor suppressor in cervical cancer in part by inhibiting activation of the NF-κB pathway.
Insights
MAFIP acts as a tumor suppressor in cervical cancer by inhibiting the NF-κB pathway. Its downregulation is linked to cervical intraepithelial neoplasia, and restoring MAFIP levels reduces tumor formation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Cervical cancer is a significant global health issue for women.
- Tumor suppressor gene inactivation is critical in cervical cancer development.
- Previous research indicated MAFIP inhibits human cervical cancer HeLa cell growth.
Purpose of the Study:
- To investigate the role of MAFIP as a tumor suppressor in cervical cancer.
- To elucidate the molecular mechanisms underlying MAFIP's function.
- To confirm MAFIP's in vivo tumor suppressor activity.
Main Methods:
- Analyzing MAFIP expression in cervical intraepithelial neoplasia tissues.
- Inducing MAFIP expression in HeLa cells and assessing tumor formation in nude mice.
- Evaluating the impact of MAFIP overexpression on the NF-κB signaling pathway components (IKK, IκBα, p65).
- Assessing the effect of MAFIP on c-myc oncogene induction.
- Utilizing siRNA to knockdown MAFIP and observe effects on cell proliferation and NF-κB activation.
Main Results:
- MAFIP expression was found to be downregulated in cervical intraepithelial neoplasia tissues.
- Induced MAFIP expression significantly inhibited tumor formation in vivo, confirming its tumor suppressor role.
- Overexpression of MAFIP suppressed NF-κB pathway activation by inhibiting key phosphorylation and degradation events.
- MAFIP overexpression impaired NF-κB-dependent c-myc induction.
- MAFIP knockdown activated the NF-κB pathway and promoted cell proliferation.
Conclusions:
- MAFIP functions as a tumor suppressor in cervical cancer.
- MAFIP inhibits cervical cancer progression, partly through the suppression of NF-κB pathway activation.
- MAFIP downregulation is associated with cervical cancer development, suggesting its potential as a therapeutic target.
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