非小细胞肺癌组织中USP22调控COX-2的研究

USP22 regulation of cyclooxygenase-2 in nonsmall cell lung cancer

组蛋白的泛素水解酶泛素特异性蛋白酶22(USP22)是一种表观遗传修饰剂,在许多肿瘤中作为致癌基因而上调.USP22在非小细胞肺癌(NSCLC)中异常表达往往预示着患者生存率低下.人类USP22基因作为致癌基因,其调控底物研究较少,在癌症中作用机制尚不清楚.本研究发现环氧合酶-2(COX-2)作为USP22直接调控底物,其在细胞中的表达水平由USP22介导的去泛素化调控.USP22沉默下调COX-2表达水平,减少其半衰期,并通过泛素化状态的调控调节COX-2的稳定性与活力,从而抑制肺癌细胞增殖.结果表明USP22可能通过对COX-2的活性和稳定性的调节在癌症发生发展中起作用.

Ubiquitin-specific protease 22（ USP22） is an epigenetic modifier that is upregulated in many cancers as an oncogene.Abnormal expression of USP22 in non- small cell lung cancer（ NSCLC） often indicates a poor survival rate. USP22 gene,as an oncogene,has little research on its regulatory substrate and its mechanism in cancer is unclear. In the study, we found that cyclooxygenase-2（ COX-2） as a substrate for direct regulation of USP22,its expression in cells regulated by USP22 mediated ubiquitination. USP22 silencing down regulate the expression of COX-2,reduce its half-life,and regulate the stability and activity of COX-2 through the regulation of ubiquitination,thereby inhibiting the proliferation of lung cancer cells. The findings of this study suggest that USP22 may play a role in the development of cancer by regulating the activity and stability of COX-2.