J Cancer 2023; 14(9):1579-1591. doi:10.7150/jca.84213 This issue Cite

Research Paper

ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM

Li Li1*, Mengting Yang1*, Xufeng Pu3*, Yu Tang4*, Fei Fei1, Zhangzuo Li1, Hanjin Hou1, Qian Chen1, Qiaowei Wang1, Yuqing Wu1, Ying Zhang1✉, Caifang Ren2✉, Aihua Gong1✉

1. Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiang Su Province, China.
2. Department of Pathology, School of Medicine, Jiangsu University, Zhenjiang, Jiang Su Province, China.
3. Department of Medical Imaging, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiang Su Province, China.
4. Department of Pathology, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiang Su Province, China.
* These authors have contributed equally to this work and share first authorship.

Citation:
Li L, Yang M, Pu X, Tang Y, Fei F, Li Z, Hou H, Chen Q, Wang Q, Wu Y, Zhang Y, Ren C, Gong A. ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM. J Cancer 2023; 14(9):1579-1591. doi:10.7150/jca.84213. https://www.jcancer.org/v14p1579.htm
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Abstract

Graphic abstract

AlkB homolog 5, RNA demethylase (ALKBH5) is abnormally highly expressed in glioblastoma multiforme (GBM) and is negatively correlated with overall survival in GBM patients. In this study, we found a new mechanism that ALKBH5 and pyrroline-5-carboxylate reductase 2 (PYCR2) formed a positive feedback loop involved in proline synthesis in GBM. ALKBH5 promoted PYCR2 expression and PYCR2-mediated proline synthesis; while PYCR2 promoted ALKBH5 expression through the AMPK/mTOR pathway in GBM cells. In addition, ALKBH5 and PYCR2 promoted GBM cell proliferation, migration, and invasion, as well as proneural-mesenchymal transition (PMT). Furthermore, proline rescued AMPK/mTOR activation and PMT after silencing PYCR2 expression. Our findings reveal an ALKBH5-PYCR2 axis linked to proline metabolism, which plays an important role in promoting PMT in GBM cells and may be a promising therapeutic pathway for GBM.

Keywords: ALKBH5, PYCR2, proline, AMPK/mTOR, PMT.


Citation styles

APA
Li, L., Yang, M., Pu, X., Tang, Y., Fei, F., Li, Z., Hou, H., Chen, Q., Wang, Q., Wu, Y., Zhang, Y., Ren, C., Gong, A. (2023). ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM. Journal of Cancer, 14(9), 1579-1591. https://doi.org/10.7150/jca.84213.

ACS
Li, L.; Yang, M.; Pu, X.; Tang, Y.; Fei, F.; Li, Z.; Hou, H.; Chen, Q.; Wang, Q.; Wu, Y.; Zhang, Y.; Ren, C.; Gong, A. ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM. J. Cancer 2023, 14 (9), 1579-1591. DOI: 10.7150/jca.84213.

NLM
Li L, Yang M, Pu X, Tang Y, Fei F, Li Z, Hou H, Chen Q, Wang Q, Wu Y, Zhang Y, Ren C, Gong A. ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM. J Cancer 2023; 14(9):1579-1591. doi:10.7150/jca.84213. https://www.jcancer.org/v14p1579.htm

CSE
Li L, Yang M, Pu X, Tang Y, Fei F, Li Z, Hou H, Chen Q, Wang Q, Wu Y, Zhang Y, Ren C, Gong A. 2023. ALKBH5-PYCR2 Positive Feedback Loop Promotes Proneural-Mesenchymal Transition Via Proline Synthesis In GBM. J Cancer. 14(9):1579-1591.

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