Zc3hav1, also known as Zinc finger CCCH-type antiviral protein 1 and PARP13 (Poly(ADP-ribose) polymerase-13), is an RNA-binding protein. It plays crucial roles in multiple biological processes. It is involved in the cytosolic DNA-sensing process by facilitating STING activation, thus enhancing the innate immune response. It also has functions in post-transcriptional regulation of RNA, affecting mRNA stability and translation, and modulating the miRNA silencing pathway [1,3].

In a study, Zc3hav1 deficiency protected mice against herpes simplex virus-1 (HSV-1) infection-or 5,6-dimethylxanthenone-4-acetic acid (DMXAA)-induced inflammation in a STING-dependent manner. This indicates that Zc3hav1 is a key regulator of STING signaling, potentiating STING activation by promoting its oligomerization and translocation from the endoplasmic reticulum to the Golgi, which activates the IRF3 and NF-κB pathway [1]. In pancreatic cancer, Zc3hav1 was found to be highly expressed in tissues and cell lines, and its overexpression accelerated cell proliferation, colony formation, migration, and invasion. Bioinformatics and immunoprecipitation assays showed that Zc3hav1 could directly bind to KRAS and positively regulate its expression, activating the MAPK signaling by increasing p-ERK levels. Conversely, knockdown of Zc3hav1 significantly reduced tumorigenesis [2].

In conclusion, Zc3hav1 is essential in regulating the innate immune response through STING signaling and is also involved in the proliferation and metastasis of pancreatic cancer. The Zc3hav1-deficient mouse models have revealed its role in protecting against HSV-1 infection-and DMXAA-induced inflammation, as well as its significance in pancreatic cancer development, providing potential therapeutic targets for STING-dependent inflammation and pancreatic cancer [1,2].

References:

1. Qin, Danhui, Song, Hui, Wang, Caiwei, Zhang, Lei, Zhang, Weifang. 2024. ZC3HAV1 facilitates STING activation and enhances inflammation. In Communications biology, 7, 1418. doi:10.1038/s42003-024-07116-2. https://pubmed.ncbi.nlm.nih.gov/39478149/

2. Huang, Wei, Hua, Hao, Xiao, Guoliang, Yang, Qin, Jin, Lu. 2021. ZC3HAV1 promotes the proliferation and metastasis via regulating KRAS in pancreatic cancer. In Aging, 13, 18482-18497. doi:10.18632/aging.203296. https://pubmed.ncbi.nlm.nih.gov/34319912/

3. Todorova, Tanya, Bock, Florian J, Chang, Paul. 2015. Poly(ADP-ribose) polymerase-13 and RNA regulation in immunity and cancer. In Trends in molecular medicine, 21, 373-84. doi:10.1016/j.molmed.2015.03.002. https://pubmed.ncbi.nlm.nih.gov/25851173/