NSD3/WHSC1L1 histone methyltransferase gene aberrations are observed in leukemia 
and in breast and lung carcinomas, suggesting that NSD3 is implicated in 
carcinogenesis. In this study we examined in human breast cancer cells the NSD3L 
isoform which contains the catalytic histone methyltransferase SET-domain. siRNA 
directed depletion of NSD3L followed by genome-wide microarray analysis 
identified NSD3L regulated genes which could be functionally linked to cellular 
signaling pathways such as cell growth, cell cycle, cell motility, 
transcription, and apoptosis. Notably up-regulated genes are the cell cycle 
regulators E2F2 and Arl2. In accordance with a function of NSD3L in cell cycle 
regulation NSD3L depletion resulted in an increase in the number of cells in the 
S and G2/M cell cycle phases. Moreover, NSD3L depletion increased the 
invasiveness of MDA-MB-231 breast cancer cells indicating that NSD3L normally 
restrain cellular metastatic potential. Together the presented data indicates 
that NSD3L is a candidate tumor suppressor.