Oncogene:VHL-HIF-2α轴诱导的SMYD3上调能够促使肾细胞肿瘤进展

2020-05-12 AlexYang MedSci原创

VHL-HIF-2α轴和上皮生长因子受体(EGFR)信号途径在肾细胞肿瘤(RCC)进展和发病机理中具有关键的作用。然而,很少有研究强调上述两个致瘤驱使因子在RCC中的关系。SET和包含MY

VHL-HIF-2α轴和上皮生长因子受体(EGFR)信号途径在肾细胞肿瘤(RCC)进展和发病机理中具有关键的作用。然而,很少有研究强调上述两个致瘤驱使因子在RCC中的关系。SET和包含MYND结构阈蛋白3(SMYD3)是一个组蛋白甲基转移酶,参与基因的转录和致瘤过程,但是其表达与功能在RCC中仍旧不清楚。

最近,有研究人员发现SMYD3表达在RCC肿瘤中显著上调,并且与晚期肿瘤阶段、组织和核等级以及更短的生存有关。SMYD3的缺失能够抑制RCC细胞增殖、定殖数量和异种种植肿瘤的形成有关,但却具有促进细胞凋亡的功能。同时,SMYD3能够与SP1一起促进EGFR的转录,并放大其下游信号活性。TCGA数据分析阐释了SMYD3在携带VHL功能缺失性变异的原发性RCC肿瘤中显著增加SMYD3的表达。研究人员进一步展示了HIF-2α能够直接结合到SMYD3启动子并诱导SMYD3的转录和表达。

最后,研究人员指出,他们鉴定了VHL/HIF-2α/SMYD3信号通路介导的EGFR超活性,SMYD3通过上述途径促进RCC进展。同时,SMYD3也是RCC的靶向治疗靶标和预后因子。

原始出处:

Cheng Liu, Li Liu, Kun Wang et al. VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR. Oncogene. 14 April 2020

 

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    2021-03-28 cy0324
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    2020-05-19 Eleven21
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    2020-05-14 wrj0126
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    2020-05-14 zsyan

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