MFng, also known as Manic Fringe, is a β1,3 -N -acetylglucosaminyltransferase that modifies Notch receptors and is involved in the Notch signaling pathway, which is crucial for cell differentiation, development, and disease processes [2,3,4,6,7,8]. MFng is of great biological importance as it has been implicated in various developmental and disease-related contexts. Genetic models, such as mouse models, are valuable for studying MFng's functions.

In osteosarcoma, MFng is an independent adverse prognostic factor for disease-free survival. High MFng expression promotes cell proliferation and inhibits apoptosis in U2OS cells, indicating its role in osteosarcoma progression [1]. In triple-negative breast cancer, MFng activates the Notch signaling and promotes cancer progression. The GATA3/miR205-5p axis can inhibit MFng transcription and reduce the malignancy of the cancer [2]. In clear cell renal cell carcinoma, MFng is highly expressed in endothelial cells. Knocking down MFng in endothelial cells leads to decreased cell viability, migration, and network formation, and also inhibits renal cancer cell migration, suggesting its role in angiogenesis and cancer cell migration [5]. In heart valve development, MFng promotes endothelial-to-mesenchymal transition (EndMT) mediated by the Notch signaling pathway. A heterozygous MFng mutation in patients with tetralogy of Fallot-pulmonary valve stenosis reduces MFng expression and hinders EndMT [6].

In conclusion, MFng plays essential roles in multiple biological processes, mainly through its modulation of the Notch signaling pathway. Its functions are revealed through model-based research, especially in relation to diseases like osteosarcoma, triple-negative breast cancer, clear cell renal cell carcinoma, and congenital heart valve defects. These findings contribute to our understanding of disease mechanisms and may offer potential therapeutic targets.

References:

1. Gao, Yi, Luo, Lili, Qu, Yuxing, Zhou, Qi. 2023. MFNG is an independent prognostic marker for osteosarcoma. In European journal of medical research, 28, 256. doi:10.1186/s40001-023-01139-x. https://pubmed.ncbi.nlm.nih.gov/37496053/

2. Mugisha, Samson, Di, Xiaotang, Wen, Doudou, Zhang, Shubing, Jiang, Hao. 2022. Upregulated GATA3/miR205-5p Axis Inhibits MFNG Transcription and Reduces the Malignancy of Triple-Negative Breast Cancer. In Cancers, 14, . doi:10.3390/cancers14133057. https://pubmed.ncbi.nlm.nih.gov/35804829/

3. Svensson, Per, Bergqvist, Ingela, Norlin, Stefan, Edlund, Helena. 2009. MFng is dispensable for mouse pancreas development and function. In Molecular and cellular biology, 29, 2129-38. doi:10.1128/MCB.01644-08. https://pubmed.ncbi.nlm.nih.gov/19223466/

4. Gong, Xun, Zheng, Chenglong, Jia, Haiying, Li, Xiaowu, Liu, Yuchen. 2023. A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment. In BMC cancer, 23, 1065. doi:10.1186/s12885-023-11545-3. https://pubmed.ncbi.nlm.nih.gov/37932706/

5. Cheng, Wei Kang, Oon, Chern Ein, Kaur, Gurjeet, Sainson, Richard C A, Li, Ji-Liang. 2022. Downregulation of Manic fringe impedes angiogenesis and cell migration of renal carcinoma. In Microvascular research, 142, 104341. doi:10.1016/j.mvr.2022.104341. https://pubmed.ncbi.nlm.nih.gov/35157839/

6. Yang, Junjie, Wang, Zhi, Zhou, Yue, Wang, Jian, Sun, Kun. 2024. Manic Fringe promotes endothelial-to-mesenchymal transition mediated by the Notch signalling pathway during heart valve development. In Journal of molecular medicine (Berlin, Germany), 103, 51-71. doi:10.1007/s00109-024-02492-y. https://pubmed.ncbi.nlm.nih.gov/39528804/

7. D'Amato, Gaetano, Luxán, Guillermo, del Monte-Nieto, Gonzalo, Jiménez-Borreguero, Luis J, de la Pompa, José Luis. 2015. Sequential Notch activation regulates ventricular chamber development. In Nature cell biology, 18, 7-20. doi:10.1038/ncb3280. https://pubmed.ncbi.nlm.nih.gov/26641715/

8. Hou, Xinghua, Tashima, Yuko, Stanley, Pamela. 2011. Galactose differentially modulates lunatic and manic fringe effects on Delta1-induced NOTCH signaling. In The Journal of biological chemistry, 287, 474-483. doi:10.1074/jbc.M111.317578. https://pubmed.ncbi.nlm.nih.gov/22081605/