Ifi30, also known as gamma-interferon-inducible lysosomal thiol reductase, is a critical enzyme. It mainly exists in immune cells and functions in reducing protein disulfide bonds in endocytosis-mediated protein degradation. It is involved in antigen presentation and immune regulation, including MHC class II-restricted antigen processing and MHC class I-restricted cross-presentation pathways of adaptive immunity. It also plays roles in angiogenesis and regulation of oxidative stress [3,7].

In cancer research, Ifi30 has been widely studied. In breast cancer, its up-regulation is associated with tumor stage and poor prognosis, and it has an interplay with the PD-L1 axis, affecting T-cell infiltration [1]. In glioma, high Ifi30 expression is an independent unfavorable prognostic factor, correlated with immune checkpoints and immunosuppressive phenotype, and it can activate the IL6-STAT6 signal pathway to decline chemotherapy sensitivity [2,4,5]. In zebrafish, knockdown of Ifi30 impairs caudal vein plexus formation, revealing its role in sprouting angiogenesis [3]. Porcine Ifi30 can inhibit PRRSV proliferation and host cell apoptosis in vitro [6].

In conclusion, Ifi30 is essential in immune regulation, angiogenesis, and oxidative stress regulation. Its study through various models, especially in cancer-related research such as breast cancer and glioma, provides insights into disease mechanisms, highlighting its potential as a therapeutic target. [1-3, 7-9]

References:

1. Li, Lei, Fei, Yinjiao, Dong, Tianfu, Liang, Mingxing, Tang, Jinhai. 2024. IFI30 as a key regulator of PDL1 immunotherapy prognosis in breast cancer. In International immunopharmacology, 133, 112093. doi:10.1016/j.intimp.2024.112093. https://pubmed.ncbi.nlm.nih.gov/38669947/

2. Liu, Xiu, Song, Chunyan, Yang, Shoubo, Chen, Feng, Li, Wenbin. 2020. IFI30 expression is an independent unfavourable prognostic factor in glioma. In Journal of cellular and molecular medicine, 24, 12433-12443. doi:10.1111/jcmm.15758. https://pubmed.ncbi.nlm.nih.gov/32969157/

3. Wang, Xiaoning, Ge, Xiaojuan, Qin, Yinyin, Liu, Dong, Chen, Changsheng. 2022. Ifi30 Is Required for Sprouting Angiogenesis During Caudal Vein Plexus Formation in Zebrafish. In Frontiers in physiology, 13, 919579. doi:10.3389/fphys.2022.919579. https://pubmed.ncbi.nlm.nih.gov/35910561/

4. Jiang, Wei, Zheng, Feifei, Yao, Taotao, Zheng, Wenjie, Yao, Ninghua. . IFI30 as a prognostic biomarker and correlation with immune infiltrates in glioma. In Annals of translational medicine, 9, 1686. doi:10.21037/atm-21-5569. https://pubmed.ncbi.nlm.nih.gov/34988195/

5. Zhu, Chen, Chen, Xin, Guan, Gefei, Cheng, Wen, Wu, Anhua. 2020. IFI30 Is a Novel Immune-Related Target with Predicting Value of Prognosis and Treatment Response in Glioblastoma. In OncoTargets and therapy, 13, 1129-1143. doi:10.2147/OTT.S237162. https://pubmed.ncbi.nlm.nih.gov/32103982/

6. Guo, Jia, Zhou, Mengjiao, Liu, Xin, Zhao, Zhihui, Sun, Boxing. 2018. Porcine IFI30 inhibits PRRSV proliferation and host cell apoptosis in vitro. In Gene, 649, 93-98. doi:10.1016/j.gene.2018.01.065. https://pubmed.ncbi.nlm.nih.gov/29366756/

7. Cacialli, Pietro, Mahony, Christopher B, Petzold, Tim, Rougemont, Anne-Laure, Bertrand, Julien Y. 2021. A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress. In Nature communications, 12, 4484. doi:10.1038/s41467-021-24831-0. https://pubmed.ncbi.nlm.nih.gov/34301940/