Zhang Dalin, Wornow Sarah, Peehl Donna M, Rankin Erinn B, Brooks James D
Department of Urology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Undergraduate Student Program, Brown University, Providence, RI, USA.
Transl Oncol. 2022 Nov;25:101518. doi: 10.1016/j.tranon.2022.101518. Epub 2022 Aug 27.
Fat mass and obesity-associated (FTO) protein, the first mA demethylase identified in 2011, regulates multiple aspects of RNA biology including splicing, localization, stability, and translation. Accumulating data show that FTO is involved in numerous physiological processes and is implicated in multiple cancers including renal cell carcinoma (RCC). However, the exact role of FTO in RCC remains controversial. 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 either a promoting or suppressive role of FTO in kidney cancers, the mechanisms of action of FTO, and recent progress in developing FTO inhibitors.
脂肪量与肥胖相关（FTO）蛋白是2011年发现的首个m⁶A去甲基化酶，它可调节RNA生物学的多个方面，包括剪接、定位、稳定性和翻译。越来越多的数据表明，FTO参与众多生理过程，并与包括肾细胞癌（RCC）在内的多种癌症有关。然而，FTO在RCC中的确切作用仍存在争议。一些研究表明，FTO表达降低与透明细胞肾细胞癌（ccRCC）患者的侵袭性临床特征和较短的总生存期相关，而另一些研究则发现，FTO抑制在体外和体内均能选择性降低VHL缺陷型ccRCC细胞的生长和存活。在此，我们综述支持FTO在肾癌中起促进或抑制作用的证据、FTO的作用机制以及FTO抑制剂开发的最新进展。
