1. Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1
- Author
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Seong Hwi Hong, Hyun Ji Hwang, Da Hyeon Son, Eun Song Kim, Sung Yul Park, and Young Eun Yoon
- Subjects
EZH2 ,Hippo pathway ,LATS1 ,renal cell carcinoma ,tazemetostat ,Biology (General) ,QH301-705.5 - Abstract
The most common type of kidney cancer in adults is renal cell carcinoma (RCC), which accounts for approximately 90% of cases. RCC is a variant disease with numerous subtypes; the most common subtype is clear cell RCC (ccRCC, 75%), followed by papillary RCC (pRCC, 10%) and chromophobe RCC (chRCC, 5%). To identify a genetic target for all subtypes, we analyzed The Cancer Genome Atlas (TCGA) databases of ccRCC, pRCC, and chromophobe RCC. Enhancer of zeste homolog 2 (EZH2), which encodes a methyltransferase, was observed to be significantly upregulated in tumors. The EZH2 inhibitor tazemetostat induced anticancer effects in RCC cells. TCGA analysis revealed that large tumor suppressor kinase 1 (LATS1), a key tumor suppressor of the Hippo pathway, was significantly downregulated in tumors; the expression of LATS1 was increased by tazemetostat. Through additional experiments, we confirmed that LATS1 plays a crucial role in EZH2 inhibition and has a negative association with EZH2. Therefore, we suggest that epigenetic control could be a novel therapeutic strategy for three subtypes of RCC.
- Published
- 2023
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