Nature: Yuan Gang and others found that the increased activity of NSD3 histoprotein methylation led to the occurrence of lung squamous cell carcinoma 

The amplification of chromosomal region 8p11-12 is a common genetic change that has been shown to be linked to the egenesis of lung squamous cell carcinoma (LUSC).
FGFR1 gene is the main candidate driver of tumor occurrence in the region.
, however, FGFR1 inhibition has been unsuccessful as a targeted treatment in clinical trial evaluations.
recently, researchers found that the gene for histoprotein H3 lysine 36 (H3K36) methyl transferase NSD3 is located in 8p11-12 amplifiers, and that the protein can act as a key regulator for LUSC tumor occurrence.
NSD3 expression is closely related to gene amplification compared to other 8p11-12 candidate LUSC drivers.
in the LUSC mouse model, the knock-off of NSD3, rather than FGFR1, reduced tumor growth and prolonged survival.
researchers also identified a LUSC-related variant, NSD3 (T1232A), which increased the catalytic activity of dmylation of H3K36 (H3K36me2) in vitro and in vivo.
dynamic analysis of the structure shows that the replacement of T1232A causes local flow changes in the entire NSD3 catalytic domain to alleviate automatic inhibition and increase the accessability of H3 substrates.
expression of NSD3 (T1232A) in the body accelerated tumor occurrence in the LUSC mouse model and reduced the overall survival rate.
the pathology of NSD3 (T1232A) to generate H3K36me2, re-plan chromatin landscape, promote cancer-causing gene expression markers.
addition, NSD3 promotes the transformation of trachea bronchblad cells and the growth of LUSC cell lines in heterogeneum transplanters by relying on their catalytic activity, and amplifies 8p11-12.
exhaustion of NSD3 from heterogeneity transplants derived from patients with original LUSCs containing NSD3 amplification or NSD3 (T1232A) coded variants can reduce tumor growth in mice.
, the researchers found that LUSC-derived foreign grafts regulated by NSD3 were highly sensitive to brominated enzyme inhibition.
therefore, the study identified NSD3 as a major 8p11-12 amplifier-related carcinogenic driver in LUSC, and suggested that NSD3 dependence makes LUSC susceptible to brominated enzyme inhibition in treatment.