GSE238257 SMYD5 regulates mRNA translation to promote gastric adenocarcinoma (GAC)

Contributors : Juhyung Park ; Jibo Wu ; Krzysztof J Szkop ; Jinho Jeong ; Dylan Husmann ; Natasha M Flores ; Joel W Francis ; Ying-Jiun C Chen ; Ana Morales Benitez ; Emily Zahn ; Shumei Song ; Jaffer A Ajani ; Linghua Wang ; Kamini Singh ; Ola Larsson ; Benjamin A Garcia ; Ivan Topisirovic ; Pawel K Mazur ; Or GozaniSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 at lysine 22 (rpL40K22me3) by the lysine methyltransferase (KMT) SMYD5 regulates mRNA translation output to promote gastric adenocarcinoma (GAC) malignant progression with lethal peritoneal ascites. A biochemical-proteomic strategy identifies the mono-ubiquitin fusion protein partner rpL40 as the principal physiologic substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprograms protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in GAC patient samples and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease including peritoneal carcinomatosis (PC). Supp...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research