Zhang Taotao, Sun Hongliang, Liu Rui, Cao Wanshuang, Zhang Tao, Li Enlai, Sun Xianchao, Wu Wangyu, Yu Dexin, Zhong Caiyun
Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, China.
Environ Toxicol. 2020 Nov;35(11):1274-1283. doi: 10.1002/tox.22992. Epub 2020 Jul 10.
Nanog plays an important role in the regulation of cancer stem cells (CSCs) which participate in tumorgenesis and progression. In renal cancer, tobacco smoke (TS) is considered a major risk factor. However, the molecular mechanism by which TS induces the development of renal CSC properties remains largely unknown. In this study, we showed that the level of Nanog was elevated in renal cell carcinoma (RCC) patients with a smoking history, and that Nanog overexpression promoted the traits of CSCs in renal cancer. We further demonstrated that a 8-week exposure of TS enhanced the formation of renal tumorspheres, increased the population of CD133-positive cells, and stimulated the expression of Nanog and CSC markers. In addition, TS was found to play a role in accelerating the cell growth transition from G1 to S phase in renal CSCs. Finally, we demonstrated that the TS-induced effects in renal CSCs could be reversed through the downregulation of Nanog. Our results suggested that Nanog plays a role in mediating TS-induced renal CSC properties. This study may provide new insights into the molecular mechanism of TS-related renal tumorigenesis, which can contribute to the future development of therapeutics for renal cancer.
Nanog在参与肿瘤发生和进展的癌症干细胞（CSCs）调控中发挥重要作用。在肾癌中，烟草烟雾（TS）被认为是主要危险因素。然而，TS诱导肾CSC特性发展的分子机制仍 largely未知。在本研究中，我们表明有吸烟史的肾细胞癌（RCC）患者中Nanog水平升高，且Nanog过表达促进肾癌中CSCs的特性。我们进一步证明，8周的TS暴露增强了肾肿瘤球的形成，增加了CD133阳性细胞的数量，并刺激了Nanog和CSC标志物的表达。此外，发现TS在加速肾CSCs从G1期到S期的细胞生长转变中起作用。最后，我们证明通过下调Nanog可逆转TS对肾CSCs的诱导作用。我们的结果表明Nanog在介导TS诱导的肾CSC特性中起作用。本研究可能为TS相关肾肿瘤发生的分子机制提供新见解，这有助于肾癌治疗的未来发展。
