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]. It is also involved in ribosome biogenesis in eukaryotes, and its promoter contains a c-Myc binding site with c-Myc directly regulating its expression levels [2,3].

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 expression of E2F target genes and of genes involved in cell cycle, growth and apoptosis [1]. In prostate cancer, knockdown of Nop16 could significantly inhibit the proliferation, migration and invasion of PC-3 cells in vitro and in vivo [2]. In hepatocellular carcinoma, knockdown of NOP16 activated the Keap/Nrf2 signalling pathway and inhibited the invasion, migration, and EMT progression of LIHC cells [3]. In nasopharyngeal carcinoma, knocking out NOP16 inhibited the proliferation, migration and invasion of NPC cells and increased apoptosis by inhibiting the RhoA/PI3K/Akt/c-Myc and IKK/IKB/NF-κB pathways [4].

In conclusion, Nop16 is a histone mimic that plays a crucial role in regulating H3K27 methylation and gene expression. Gene knockout studies in various cancer models have revealed its significant contribution to cancer-related biological processes such as cell proliferation, migration, invasion, and apoptosis, highlighting its potential as a prognostic biomarker and therapeutic target in cancers like breast, prostate, hepatocellular, and nasopharyngeal carcinomas.