2020年9月1日 · Integrated analysis of transcriptome-wide m 6 A-seq and mRNA-seq analysis identified the glutamine transporter SLC1A5 as an FTO target that promotes metabolic reprogramming and survival of VHL-deficient ccRCC cells. These findings identify FTO as a potential HIF-independent therapeutic target for the treatment of …

2020年8月19日 · Here we report a synthetic lethal interaction between the epitranscriptomic modifier FTO and the tumor suppressor VHL. Notably, FTO inhibition reduced the growth of both HIF wild type and HIF-deficient tumors.

2024年9月27日 · VHL是ccRCC中最重要的肿瘤抑制因子，VHL的Co-IP实验发现VHL与METTL3、METTL14和WTAP相互作用 (图1F)。 METTL3或METTL14的Co-IP实验也证实了其与VHL相互作用 (图1、G和H)，VHL与m6A调控之间有潜在联系。 体外表达的GST-pull-down实验也揭示了VHL与METTL3或METTL14之间的相互作用 (图1I)。 VHL E3连接酶结构域可能对调节METTL3/14复合物的形成很重要。 为研究VHL是否可以调节肾细胞中的m6A水平。 在HKC和293T细胞中用2种 …

何川与陈建军教授的脚步并未停留在Cell的研究上，近日，他们联手在Molecular Cell发表研究：Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm，该研究是目前最全面的关于FTO介导的RNA 去甲基化研究。

2022年11月1日 · Some studies demonstrated that decreased FTO expression was associated with aggressive clinical features and shorter overall survival in clear cell RCC (ccRCC) patients, while others found that FTO inhibition selectively reduced the growth and survival of VHL-deficient ccRCC cells in vitro and in vivo. Here, we review the evidence supporting ...

Genetic inactivation of FTO using multiple orthogonal approaches revealed that FTO inhibition selectively reduces the growth and survival of VHL-deficient cells in vitro and in vivo. Notably, FTO inhibition reduced the survival of both HIF wild type and HIF-deficient tumors, identifying FTO as an HIF-independent vulnerability of VHL-deficient ...

Using this approach, we identified a synthetic lethal interac-tion between VHL and the m6A RNA demethylase FTO in renal cell carcinoma. MiSL identified FTO as a synthetic lethal partner of VHL because deletions of FTO are mutually exclusive with VHL loss in pan cancer datasets.

2024年11月4日 · In clear cell renal cell carcinoma (ccRCC), for example, FTO loss has been shown to limit glutamine consumption and suppress the survival of VHL-deficient cells, in part by facilitating the decay of the SLC1A5 transcript .

2024年4月15日 · Whether VHL regulates FTO protein’s function and its underlying mechanism remain to be investigated. Our study further demonstrates that VHL depletion results in altered mRNA stability of target genes, including PIK3R3. PIK3R3 mRNA displayed accelerated decay upon VHL depletion, suggesting that VHL plays a role in stabilizing target mRNAs ...

2020年9月1日 · Here we report a synthetic lethal interaction between the epitranscriptomic modifier FTO and the tumor suppressor VHL. Notably, FTO inhibition reduced the growth of both HIF wild type and HIF-deficient tumors.