Tang Xiaodong, Liu Shuanghai, Chen Dawei, Zhao Zhenguo, Zhou Jiahua
Department of Hepatobiliary Surgery, The Affiliated Jiangyin Hospital of Southeast University Medical College, Wuxi, Jiangsu 214400, P.R. China.
Department of Hepatic-Biliary-Pancreatic Center, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Oncol Lett. 2019 Feb;17(2):2473-2478. doi: 10.3892/ol.2018.9873. Epub 2018 Dec 28.
Fat mass and obesity-associated (FTO) protein has been identified as a critical demethylase in regulating cellular mRNA stability by removing N-methyladenosine (mA) residues in mRNA. Even though the role of FTO in body energy metabolism has been well established, its role in cancer cell homeostasis remains unclear. In the present study, by using RNA interference, it was indicated that FTO is required for pancreatic cancer cell proliferation. Knockdown of FTO resulted in compromised proliferation of pancreatic cancer cells. Furthermore, DNA synthesis was compromised, followed by an increase in apoptosis in FTO small interfering RNA (siRNA)-treated cells. In terms of its underlying mechanism, FTO has been indicated to interact with MYC proto-oncogene, bHLH transcription factor and to enhance its stability by decreasing its mA level. Therefore, the aforementioned observations indicate a novel mechanism for the regulation of pancreatic cancer cells by FTO, which may provide insight on pancreatic cancer treatment strategies.
脂肪量与肥胖相关（FTO）蛋白已被确定为一种关键的去甲基化酶，可通过去除mRNA中的N-甲基腺苷（mA）残基来调节细胞mRNA稳定性。尽管FTO在机体能量代谢中的作用已得到充分证实，但其在癌细胞内稳态中的作用仍不清楚。在本研究中，通过RNA干扰表明，FTO是胰腺癌细胞增殖所必需的。敲低FTO导致胰腺癌细胞增殖受损。此外，DNA合成受到影响，随后在FTO小干扰RNA（siRNA）处理的细胞中细胞凋亡增加。就其潜在机制而言，FTO已被证明可与MYC原癌基因、bHLH转录因子相互作用，并通过降低其mA水平来增强其稳定性。因此，上述观察结果表明了FTO调节胰腺癌细胞的一种新机制，这可能为胰腺癌的治疗策略提供见解。
