Duan Xiaoran, Yang Li, Wang Liuya, Liu Qinghua, Zhang Kai, Liu Shasha, Liu Chaojun, Gao Qun, Li Lifeng, Qin Guohui, Zhang Yi
Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, P.R. China.
Internet Medical and System Applications of National Engineering Laboratory, Zhengzhou, 450052, Henan, P.R. China.
Cell Biosci. 2022 May 14;12(1):60. doi: 10.1186/s13578-022-00798-3.
Epitranscriptomics studies have contributed greatly to the development of research on human cancers. In recent years, N6-methyladenosine (m6A), an RNA modification on the N-6 position of adenosine, has been found to play a potential role in epigenetic regulation. Therefore, we aimed to evaluate the regulation of cancer progression properties by m6A.
We found that m6A demethylase fat mass and obesity-associated protein (FTO) was highly expressed in esophageal cancer (EC) stem-like cells, and that its level was also substantially increased in EC tissues, which was closely correlated with a poor prognosis in EC patients. FTO knockdown significantly inhibited the proliferation, invasion, stemness, and tumorigenicity of EC cells, whereas FTO overexpression promoted these characteristics. Furthermore, integrated transcriptome and meRIP-seq analyses revealed that HSD17B11 may be a target gene regulated by FTO. Moreover, FTO promoted the formation of lipid droplets in EC cells by enhancing HSD17B11 expression. Furthermore, depleting YTHDF1 increased the protein level of HSD17B11.
These data indicate that FTO may rely on the reading protein YTHDF1 to affect the translation pathway of the HSD17B11 gene to regulate the formation of lipid droplets in EC cells, thereby promoting the development of EC. The understanding of the role of epitranscriptomics in the development of EC will lay a theoretical foundation for seeking new anticancer therapies.
表观转录组学研究对人类癌症研究的发展做出了巨大贡献。近年来，已发现N6-甲基腺苷（m6A），一种腺苷N-6位的RNA修饰，在表观遗传调控中发挥潜在作用。因此，我们旨在评估m6A对癌症进展特性的调控作用。
我们发现m6A去甲基化酶脂肪量和肥胖相关蛋白（FTO）在食管癌（EC）干细胞样细胞中高表达，并且其水平在EC组织中也显著升高，这与EC患者的不良预后密切相关。FTO敲低显著抑制EC细胞的增殖、侵袭、干性和致瘤性，而FTO过表达则促进这些特性。此外，综合转录组和meRIP-seq分析表明，HSD17B11可能是受FTO调控的靶基因。此外，FTO通过增强HSD17B11表达促进EC细胞中脂滴的形成。此外，敲低YTHDF1可增加HSD17B11的蛋白水平。
这些数据表明，FTO可能依赖于阅读蛋白YTHDF1来影响HSD17B11基因的翻译途径，从而调节EC细胞中脂滴的形成，进而促进EC的发展。对表观转录组学在EC发展中作用的理解将为寻找新的抗癌疗法奠定理论基础。
