Nop16-KO Mouse

Nop16, also known as HSPC111, is an evolutionarily conserved and ubiquitously expressed endogenous mammalian protein. It functions as a H3K27 mimic, binding to EED in the H3K27 trimethylation PRC2 complex and to the H3K27 demethylase JMJD3, thus regulating Histone H3K27 methylation and gene repression [1]. Nop16 is involved in various biological processes and is associated with multiple diseases.

In breast cancer, Nop16 knockout selectively globally increases H3K27me3, a heterochromatin mark. Depletion of Nop16 in breast cancer cell lines causes cell cycle arrest, decreases cell proliferation, and selectively decreases the expression of E2F target genes and genes involved in cell cycle, growth, and apoptosis. Conversely, ectopic Nop16 expression in triple-negative breast cancer cell lines promotes cell proliferation, migration, invasivity in vitro, and tumor growth in vivo [1]. In prostate cancer, knocking down Nop16 significantly inhibits the proliferation, migration, and invasion of PC-3 cells in vitro and in vivo, and low expression of Nop16 reduces total protein synthesis and induces apoptosis [2]. In hepatocellular carcinoma, knockdown of Nop16 activates the Keap/Nrf2 signalling pathway and inhibits the invasion, migration, and EMT progression of LIHC cells [3]. In nasopharyngeal carcinoma, knocking out Nop16 inhibits the proliferation, migration, and invasion of NPC cells and increases apoptosis by inhibiting the RhoA/PI3K/Akt/c-Myc and IKK/IKB/NF-κB signalling pathways [5]. In Cryptococcus deuterogattii, Nop16 is required for extracellular vesicle (EV) production, and deletion of Nop16 leads to a reduced number of EVs, an altered small-molecule composition, and hypovirulence [4].

In conclusion, Nop16 plays a crucial role in regulating histone H3K27 methylation and gene expression. Through gene knockout studies in various cell lines and animal models, it has been shown to be involved in the development and progression of multiple cancers, such as breast, prostate, hepatocellular, and nasopharyngeal carcinomas. In addition, it is essential for EV biogenesis and virulence in Cryptococcus deuterogattii. Understanding the function of Nop16 provides potential therapeutic targets for these diseases.

References:

1. Takashima, Ken, Lee, Dian-Jang, Trovero, María Fernanda, Lieberman, Judy, Greer, Eric Lieberman. 2023. NOP16 is a histone mimetic that regulates Histone H3K27 methylation and gene repression. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.06.13.544862. https://pubmed.ncbi.nlm.nih.gov/37397991/

2. Yang, Tong, Sun, Fengliang, Zhang, Changwen, Xu, Yong, Liu, Qian. . Elevated Expression of NOP16 as a Novel Prognostic Biomarker of Prostate Cancer. In Annals of clinical and laboratory science, 53, 587-597. doi:. https://pubmed.ncbi.nlm.nih.gov/37625836/

3. Mu, Shangdong, Tian, Qiusi, Shen, Liangyu. . NOP16 promotes hepatocellular carcinoma progression and triggers EMT through the Keap1-Nrf2 signaling pathway. In Technology and health care : official journal of the European Society for Engineering and Medicine, 32, 2463-2483. doi:10.3233/THC-231256. https://pubmed.ncbi.nlm.nih.gov/38251077/

4. Castelli, Rafael F, Pereira, Alana, Honorato, Leandro, Fill, Taícia P, Rodrigues, Marcio L. 2022. Extracellular Vesicle Formation in Cryptococcus deuterogattii Impacts Fungal Virulence and Requires the NOP16 Gene. In Infection and immunity, 90, e0023222. doi:10.1128/iai.00232-22. https://pubmed.ncbi.nlm.nih.gov/35862719/

5. Xiong, Wenmin, Li, Daojing, Ao, Fenghua, Tu, Ziwei, Xiong, Jianping. . The role and molecular mechanism of NOP16 in the pathogenesis of nasopharyngeal carcinoma. In Cell biochemistry and function, 42, e3939. doi:10.1002/cbf.3939. https://pubmed.ncbi.nlm.nih.gov/38454810/