FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation

Xu, Xingyan; Zhuang, Xuefen; Yu, Haowei; Li, Ping; Li, Xiaosa; Lin, Huiping; Teoh, Jian-peng; Chen, Yiwen; Yang, Yuanlan; Cheng, Yang; Chen, Weiyu; Fu, Xiaodong

doi:10.7150/thno.94161

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2024; 14(5):2151-2166. doi:10.7150/thno.94161 This issue Cite

Research Paper

FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation

Xingyan Xu^1#, Xuefen Zhuang^1#, Haowei Yu^1#, Ping Li¹, Xiaosa Li¹, Huiping Lin¹, Jian-peng Teoh¹, Yiwen Chen¹, Yuanlan Yang¹, Yang Cheng^3✉, Weiyu Chen^1✉, Xiaodong Fu^1,2✉

1. Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
2. Department of Gynecology and Obstetrics, The Sixth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
3. Department of Gynecology and Obstetrics, Guangzhou First People's Hospital, Guangzhou, China.
^#Equal contribution

Citation:

Xu X, Zhuang X, Yu H, Li P, Li X, Lin H, Teoh Jp, Chen Y, Yang Y, Cheng Y, Chen W, Fu X. FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation. Theranostics 2024; 14(5):2151-2166. doi:10.7150/thno.94161. https://www.thno.org/v14p2151.htm

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Abstract

Background: The therapeutic benefits of targeting follicle-stimulating hormone (FSH) receptor in treatment of ovarian cancer are significant, whereas the role of FSH in ovarian cancer progresses and the underlying mechanism remains to be developed.

Methods: Tissue microarray of human ovarian cancer, tumor xenograft mouse model, and in vitro cell culture were used to investigate the role of FSH in ovarian carcinogenesis. siRNA, lentivirus and inhibitors were used to trigger the inactivation of genes, and plasmids were used to increase transcription of genes. Specifically, pathological characteristic was assessed by histology and immunohistochemistry (IHC), while signaling pathway was studied using western blot, quantitative RT-PCR, and immunofluorescence.

Results: Histology and IHC of human normal ovarian and tumor tissue confirmed the association between FSH and Snail in ovarian cancer metastasis. Moreover, in epithelial ovarian cancer cells and xenograft mice, FSH was showed to promote epithelial mesenchymal transition (EMT) progress and metastasis of ovarian cancer via prolonging the half-life of Snail mRNA in a N6-methyladenine methylation (m6A) dependent manner, which was mechanistically through the CREB/ALKBH5 signaling pathway.

Conclusions: These findings indicated that FSH induces EMT progression and ovarian cancer metastasis via CREB/ALKBH5/Snail pathway. Thus, this study provided new insight into the therapeutic strategy of ovarian cancer patients with high level of FSH.

Keywords: Follicle-stimulating hormone, Epithelial ovarian cancer, Epithelial-mesenchymal transition, Snail, ALKBH5

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APA

Xu, X., Zhuang, X., Yu, H., Li, P., Li, X., Lin, H., Teoh, J.p., Chen, Y., Yang, Y., Cheng, Y., Chen, W., Fu, X. (2024). FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation. Theranostics, 14(5), 2151-2166. https://doi.org/10.7150/thno.94161.

ACS

Xu, X.; Zhuang, X.; Yu, H.; Li, P.; Li, X.; Lin, H.; Teoh, J.p.; Chen, Y.; Yang, Y.; Cheng, Y.; Chen, W.; Fu, X. FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation. Theranostics 2024, 14 (5), 2151-2166. DOI: 10.7150/thno.94161.

NLM

CSE

Xu X, Zhuang X, Yu H, Li P, Li X, Lin H, Teoh Jp, Chen Y, Yang Y, Cheng Y, Chen W, Fu X. 2024. FSH induces EMT in ovarian cancer via ALKBH5-regulated Snail m6A demethylation. Theranostics. 14(5):2151-2166.

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