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Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage
Miaomiao Huang1,2,3,4,5,6, Jingjing Hu1,2,3,4,5,6, Yueran Chen1
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, Anhui, China.
Background:
Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored.
Methods And Results:
Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo.
Conclusion:
Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) inhibits cervical cancer progression. MANF-silenced macrophages promote tumor growth, suggesting MANF as a therapeutic target.
Area of Science:
- Oncology
- Immunology
Background:
- Cervical cancer progression factors remain unclear.
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) is known for anti-inflammatory properties and macrophage regulation.
Purpose of the Study:
- To explore the effect and mechanism of MANF in cervical cancer.
- To investigate MANF's role in regulating macrophage polarization in cervical cancer.
Main Methods:
- Immunohistochemistry and western blot for MANF expression.
- qRT-PCR for MANF mRNA levels.
- Dual-labeled immunofluorescence to locate MANF in macrophages.
- In vitro assays with MANF-silenced macrophages and cervical cancer cells (HeLa, SiHa).
- In vivo tumor formation assay in nude mice.
Main Results:
- MANF was highly expressed in peritumoral tissues and primarily located in macrophages.
- MANF-silenced macrophages promoted cervical cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) via NF-κB signaling.
- MANF-silenced macrophages enhanced cervical tumor formation in vivo.
Conclusions:
- MANF exhibits an inhibitory role in cervical cancer progression.
- MANF represents a potential therapeutic target for cervical cancer treatment.
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