Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, South Korea; Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea.
Biochem Biophys Res Commun. 2020 Jul 23;528(2):376-382. doi: 10.1016/j.bbrc.2020.01.011. Epub 2020 Feb 19.
The RNA binding proteins (RBPs) have multiple roles in human cancer. However, their molecular target and function have not been clearly identified. Our genomic analysis derived from patients reveals that NONO is a potential oncogenic gene in lung cancer. NONO is highly expressed in lung cancer tissues compared with normal tissues, and its expression has been correlated with the prognosis of lung cancer patients. We found that NONO significantly influences cancer cell proliferation in lung cancer. Gene expression profiles with NONO-depleted cells revealed that the sirtuin signaling pathway is highly correlated with NONO. Thus, NONO-silenced cells caused reduction of the TCA cycle and glycolysis metabolism. We identified that NONO regulated NAMPT, which is a well-known gene involved in sirtuin signaling, and NONO has a significant correlation with NAMPT in lung cancer patients. We propose that NONO modulates energy metabolism by direct interaction with NAMPT and suggest that a functional relationship between NONO and NAMPT contributes to lung cancer cell survival. Targeting the axis can be a promising approach for patient treatment in lung cancer.
RNA 结合蛋白 (RBPs) 在人类癌症中具有多种作用。然而，它们的分子靶标和功能尚未明确确定。我们从患者中得出的基因组分析表明，NONO 是肺癌中的潜在致癌基因。NONO 在肺癌组织中的表达明显高于正常组织，其表达与肺癌患者的预后相关。我们发现 NONO 显著影响肺癌细胞的增殖。用 NONO 耗尽的细胞进行的基因表达谱分析表明，沉默信息调节因子信号通路与 NONO 高度相关。因此，NONO 沉默的细胞导致三羧酸循环和糖酵解代谢减少。我们鉴定出 NONO 调节 NAMPT，NAMPT 是参与沉默信息调节因子信号通路的众所周知的基因，NONO 与肺癌患者中的 NAMPT 具有显著相关性。我们提出 NONO 通过与 NAMPT 的直接相互作用来调节能量代谢，并表明 NONO 和 NAMPT 之间的功能关系有助于肺癌细胞的存活。针对该轴可能是治疗肺癌患者的一种有前途的方法。
