NSUN6, short for Nop2/Sun RNA methyltransferase family member 6, is an RNA 5-methylcytosine (m5C) methyltransferase. It is involved in the m5C modification of RNAs, including mRNA and tRNA. This modification participates in various biological processes such as translation termination, and is potentially part of a quality control mechanism [2]. NSUN6-mediated m5C modification also impacts different signaling pathways and is associated with many diseases, highlighting its biological importance. Genetic models, like knockout models, can be valuable to further explore its functions.

In cervical cancer, NSUN6 overexpression promotes radioresistance by mediating the m5C modification of NDRG1 mRNA, which in turn enhances NDRG1 mRNA stability and homologous recombination-mediated DNA repair [1]. In colon adenocarcinoma, high NSUN6 expression is associated with shorter survival, and it promotes cell cycle progression and cell proliferation by upregulating METTL3 and catalyzing its m5C modification [3]. In lung cancer, NSUN6 expression is reduced, and over-expression of it restricts cell proliferation, migration, and epithelial-mesenchymal transition by regulating NM23-H1 expression in an m5C-dependent manner [4]. In osteosarcoma, NSUN6 is upregulated, and its loss reduces cell proliferation, migration, and invasion by down-regulating EEF1A2 expression and inhibiting the Akt/mTOR signaling pathway via m5C methylation [5].

In summary, NSUN6 is a crucial m5C methyltransferase. Through model-based research, it has been shown to play significant roles in multiple disease areas, such as cancer. These studies using loss-of-function models have revealed its functions in promoting or inhibiting cancer cell behaviors, which helps in understanding the disease mechanisms and may provide potential therapeutic targets.