Marchf3-KO Mouse

MARCHF3, also known as membrane-associated ring-CH-type finger 3, is involved in multiple biological processes. It has a role in ubiquitination, a process that tags proteins for degradation or other regulatory functions. Ubiquitination pathways are crucial in regulating various cellular functions, including immune responses, cell death, and protein homeostasis [2,3].

In hepatocellular carcinoma (HCC), MARCHF3 was identified in transcriptomic profiles of tumors with different responses to immune checkpoint inhibitors (ICIs). MARCHF3 was significantly upregulated in tumors from patients who responded to ICIs. It directly interacted with Poly(ADP-Ribose) Polymerase 1 (PARP1) via K48-linked ubiquitination, leading to PARP1 degradation. This promoted double-strand DNA release, activated cCAS-STING in dendritic cells, and augmented tumor control [1].

In Alzheimer's disease, Bushen Huoxue acupuncture ameliorated the disease by upregulating MARCHF3, which induced NLRP3 ubiquitination and inhibited caspase-1-dependent pyroptosis [2].

In trypanosomiasis-affected dromedary camels, the MARCHF3 gene was significantly up-regulated [4].

In ovarian cancer, MARCHF3 was among three genes selected to develop a prognostic model based on sphingolipid-related genes (SRGs), with higher risk scores related to shorter overall survival [5].

In summary, MARCHF3 is a key regulator involved in multiple disease conditions. In HCC, it plays a role in regulating antitumor immunity related to ICI response. In Alzheimer's disease, it helps inhibit pyroptosis. In trypanosomiasis-affected camels, it shows differential expression, and in ovarian cancer, it is part of a prognostic model. These findings from various disease-based studies highlight the importance of MARCHF3 in understanding disease mechanisms and potential prognoses.

References:

1. Cao, Jun, Su, Bingbing, Zhang, Chi, Wang, Qian, Bai, Dou-Sheng. 2024. Degradation of PARP1 by MARCHF3 in tumor cells triggers cCAS-STING activation in dendritic cells to regulate antitumor immunity in hepatocellular carcinoma. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2024-010157. https://pubmed.ncbi.nlm.nih.gov/39608977/

2. Zhu, Hong, Zhang, Ting, Li, Ruomeng, Xu, Jiangxi, Xiao, Lan. 2024. Bushen Huoxue acupuncture ameliorates Alzheimer's disease by upregulating MARCHF3 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis. In Metabolic brain disease, 40, 11. doi:10.1007/s11011-024-01459-9. https://pubmed.ncbi.nlm.nih.gov/39556273/

3. Wang, Xian, Jiang, Ling, Liu, Xue-Qi, Zhu, Qi-Jin, Wu, Yong-Gui. 2022. Identification of Genes Reveals the Mechanism of Cell Ferroptosis in Diabetic Nephropathy. In Frontiers in physiology, 13, 890566. doi:10.3389/fphys.2022.890566. https://pubmed.ncbi.nlm.nih.gov/35721535/

4. Elsayed, Ahmed A, Barghash, Safaa M, El-Kattan, Adel M, Osman, Wafaa A, Ateya, Ahmed I. 2024. Analysis of potential genes, immunological and antioxidant profiles associated with trypanosomiasis susceptibility in dromedary camels. In Veterinary parasitology, 331, 110264. doi:10.1016/j.vetpar.2024.110264. https://pubmed.ncbi.nlm.nih.gov/39059159/

5. Huang, Xu, Li, Xiaoyu, Shan, Wulin, Peng, Wenju, Xia, Bairong. 2025. Integrating Single-Cell and Bulk RNA Sequencing Data to Explore Sphingolipid Metabolism Molecular Signatures in Ovarian Cancer Prognosis: an Original Study. In International journal of medical sciences, 22, 1958-1977. doi:10.7150/ijms.107391. https://pubmed.ncbi.nlm.nih.gov/40225866/