Rnf114-KO Mouse

RNF114, also known as E3 ubiquitin ligase RING finger protein 114, is an E3 ubiquitin ligase involved in multiple biological processes. It participates in the DNA damage response as a PARylation-dependent enzyme, where it targets PARP1 for degradation [1]. It is also associated with the regulation of cell proliferation, metastasis in cancers, and early embryo development [2,3,4,5]. Genetic models such as gene knockout could potentially help further elucidate its functions.

In loss-of-function studies, silencing RNF114 in gastric cancer cells suppressed their proliferation and metastasis, suggesting its oncogenic role in this cancer type [2]. In colorectal cancer, knockdown of RNF114 diminished the proliferation, stemness, invasion, and wound healing of cancer cells, and also facilitated apoptosis both in vitro and in vivo [3]. Depletion of maternal RNF114 in mouse embryos led to developmental arrest at the two-cell stage, indicating its crucial role in zygotic genome activation [4].

In conclusion, RNF114 is an important E3 ubiquitin ligase involved in DNA damage response, cancer cell behaviors, and embryo development. Studies using gene knockout or knockdown models have revealed its oncogenic role in gastric and colorectal cancers, as well as its significance in mouse embryo development, providing potential therapeutic targets for cancer treatment and insights into embryo development mechanisms.

References:

1. Li, Peng, Zhen, Yuanli, Kim, Chiho, Qin, Tian, Yu, Yonghao. 2023. Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in BRCA-mutated cancer. In Science advances, 9, eadg7752. doi:10.1126/sciadv.adg7752. https://pubmed.ncbi.nlm.nih.gov/37878693/

2. Feng, Zongfeng, Li, Leyan, Zeng, Qingwen, Cao, Yi, Li, Zhengrong. 2022. RNF114 Silencing Inhibits the Proliferation and Metastasis of Gastric Cancer. In Journal of Cancer, 13, 565-578. doi:10.7150/jca.62033. https://pubmed.ncbi.nlm.nih.gov/35069903/

3. Liu, Shi-Cheng, Gong, Le-Lan, Huang, Feng-Chang, Liu, Xi-Hong, Li, Wen-Liang. 2023. RNF114 facilitates the proliferation, stemness, and metastasis of colorectal cancer. In Pathology, research and practice, 248, 154716. doi:10.1016/j.prp.2023.154716. https://pubmed.ncbi.nlm.nih.gov/37523804/

4. Zhou, Shuai, Guo, Yueshuai, Sun, Haifeng, Guo, Xuejiang, Huo, Ran. 2021. Maternal RNF114-mediated target substrate degradation regulates zygotic genome activation in mouse embryos. In Development (Cambridge, England), 148, . doi:10.1242/dev.199426. https://pubmed.ncbi.nlm.nih.gov/34104941/

5. da Silva, Zigomar, Glanzner, Werner Giehl, Gutierrez, Karina, Gonçalves, Paulo Bayard Dias, Bordignon, Vilceu. 2023. DCAF13 and RNF114 participate in the regulation of early porcine embryo development. In Reproduction (Cambridge, England), 166, 401-410. doi:10.1530/REP-23-0230. https://pubmed.ncbi.nlm.nih.gov/37855431/