组蛋白甲基转移酶SETD2在肾细胞癌发生中的作用机制

Mechanism of Histone Methyltransferase SETD2 in Renal Cell Carcinogenesis

肾细胞癌是一种具有复杂遗传背景的癌症,研究表明,异常的表观遗传调控是肾细胞癌发生的主要原因之一。组蛋白甲基转移酶SETD2是一种重要的表观遗传分子,并且在肾细胞癌中具有很高的突变率。为了探究SETD2在肾细胞癌发生与发展中的作用和机制,该研究利用肾脏特异性敲除SETD2的基因小鼠模型与肾细胞癌表型分析,发现在VHL缺失的条件下,SETD2的缺失能够导致肾细胞癌的发生。转录组测序结果显示,SETD2的敲除导致了Wnt/β-catenin与FoxO信号通路的激活。该研究为肾细胞癌的治疗提供了新的靶点和思路。

Renal cell carcinoma is a cancer with a complex genetic background,and studies have shown that aberrant epigenetic regulation is one of the major causes of renal cell carcinogenesis.Histone methyltransferase SETD2 is an important epigenetic molecule and has a high mutation rate in renal cell carcinoma.To investigate the role and mechanism of SETD2 in the development of renal cell carcinoma,this study used a mouse model of kidney-specific knockout of SETD2 with renal cell carcinoma phenotype analysis,and found that deletion of SETD2 in VHL-deficient conditions could lead to renal cell carcinoma development.According to the transcriptome sequencing results,SETD2 knockdown led to the activation of Wnt/β-catenin and FoxO signaling pathways.This study provides new therapeutic targets and therapeutic ideas for the treatment of renal cell carcinoma.