Lv Xiao-bin, Liu Lijuan, Cheng Chun, Yu Bentong, Xiong Longxin, Hu Kaishun, Tang Jianjun, Zeng Lei, Sang Yi
Nanchang Key Laboratory of Cancer Pathogenesis and Translational Research, Center Laboratory, the Third Affiliated Hospital, Nanchang University, Nanchang, China.
Department of Pharmacy, Jiangxi cancer Hospital, Nanchang, China.
Sci Rep. 2015 Dec 10;5:17940. doi: 10.1038/srep17940.
SUN2, a key component of LINC (linker of nucleoskeleton and cytoskeleton) complex located at the inner nuclear membrane, plays unknown role in lung cancer. We found that SUN2 expression was decreased in lung cancer tissue compared with paired normal tissues and that higher SUN2 levels predicted better overall survival and first progression survival. Overexpression of SUN2 inhibits cell proliferation, colony formation and migration in lung cancer, whereas knockdown of SUN2 promotes cell proliferation and migration. Additionally, SUN2 increases the sensitivity of lung cancer to cisplatin by inducing cell apoptosis. Mechanistically, we showed that SUN2 exerts its tumor suppressor functions by decreasing the expression of GLUT1 and LDHA to inhibit the Warburg effect. Finally, our results provided evidence that SIRT5 acts, at least partly, as a negative regulator of SUN2.Taken together, our findings indicate that SUN2 is a key component in lung cancer progression by inhibiting the Warburg effect and that the novel SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer.
SUN2是位于内核膜的LINC（核骨架与细胞骨架连接物）复合体的关键组成部分，在肺癌中发挥着未知作用。我们发现，与配对的正常组织相比，肺癌组织中SUN2表达降低，且较高的SUN2水平预示着更好的总生存期和首次进展生存期。SUN2的过表达抑制肺癌细胞的增殖、集落形成和迁移，而敲低SUN2则促进细胞增殖和迁移。此外，SUN2通过诱导细胞凋亡增加肺癌对顺铂的敏感性。机制上，我们表明SUN2通过降低GLUT1和LDHA的表达来抑制瓦伯格效应，从而发挥其肿瘤抑制功能。最后，我们的结果证明SIRT5至少部分作为SUN2的负调节因子发挥作用。综上所述，我们的研究结果表明，SUN2通过抑制瓦伯格效应是肺癌进展的关键组成部分，并且新的SIRT5/SUN2轴可能被证明对开发治疗肺癌患者的新策略有用。
