Researchers have discovered that SMYD2, an oncogene, aggravates and accelerates gastrointestinal stromal tumors (GISTs), and published their findings in Cell Death Discovery

Around 1 in 5 patients with GISTs present with metastasis at diagnosis, usually to the liver or throughout the serosa of the abdomen. Studies show that patients with GISTs typically demonstrate high resistance to conventional chemotherapy and radiotherapy, meaning that the prognosis is poor.

Scientists have observed that post-translational modification plays an important role in tumorigenesis in various cancers. For example, the enhancer of zoster homolog 2 (EZH2) is a transcriptional regulator that plays a key role in histone H3 lysine 27 trimethylation.


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While EZH2 has been found to play an essential role in multiple malignancies, its role in GIST remains unclear. In breast cancer, for example, EZH2 results in the down-regulation of TET1, diminishing p53 expression.

Read more about GIST etiology 

The authors of the study hypothesized that the oncogene SMYD2, which is associated with a range of tumors, mediates EZH2 methylation and plays a crucial role in the pathogenesis of GIST by regulating the TET1/p53 axis. 

The research team collected GIST and adjacent normal tissues from 46 patients. These samples were analyzed for the expression and interactions of EZH2, SMYD2, and TET1.

The authors of the study discovered that the silencing of EZH2 limited the proliferation of GIST cells. In addition, SMYD2 inhibition decreased the expression of EZH2, which facilitated the senescence of GIST cells. EZH2 was in turn discovered to diminish TET1 expression. In summary, the researchers reported that EZH2 expression positively correlated with SMYD2 expression and inversely correlated with TET1 expression in GIST tissues.

“The stabilized EZH2 subsequently participated in the promotion of cell proliferation and suppression of cell senescence in GIST by blocking TET1 and downstream p53 signaling pathways,” the researchers said. “Thereby, our results further broaden our understanding of the pathogenesis of GIST, and support the use of SMYD2 and EZH2 as potential therapeutic targets for GIST.”

Reference

Ji Y, Xu X, Long C, et al. SMYD2 aggravates gastrointestinal stromal tumor via upregulation of EZH2 and downregulation of TET1Cell Death Discov. 2022;8(1):274. doi:10.1038/s41420-022-01038-w