A novel, druggable casacade links methionine metabolism to epigenomic reprogramming in squamous cancer

DNA and histone methylation represents perhaps the most significant form of epigenetic regulation in mammalian cells, and their deregulation is most notable and pervasive in cancer. Based on our previous study which demonstrated the interplay between cancer metabolism and epigenetic regulation and the public database showing abnormal expression of LAT1 in upper aerodigestive squamous cell carcinoma (UASCC), we aim to investigate the role of LAT1 as a regulator of epigenomic reprogramming in UASCC. To identify the effect of the blockade of LAT1 on epigenetic regulation, we silenced LAT1 in UASCC cell line and performed RNA-Seq. In addition, we confirmed that Knockdown of LAT1 is associated with the downstream genes of EZH2. Therefore, we performed RNA-Seq after silencing EZH2 by transfection of siRNA and Cut&Tag assays using EZH2 and H3K27me3 antibodies KYSE510 and FADU cell lines were cultured and Cut&Tag assays were performed using the EZH2 antibody. KYSE510 cells silenced either LAT1 or EZH2 using two independent siRNA were generated to profile the transcriptome through deep sequencing.