Ma Xingjie, Qi Weibo, Yang Fan, Pan Huan
Department of Cardiothoracic Surgery, First Affiliated Hospital of Jiaxing University Jiaxing 314001, Zhejiang, China.
Department of Central Laboratory, First Affiliated Hospital of Jiaxing University Jiaxing 314001, Zhejiang, China.
Am J Transl Res. 2022 Jul 15;14(7):4549-4561. eCollection 2022.
Lung cancer is the leading cause of cancer-related mortality, and the deaths are mostly attributed to distant metastasis. Previous studies have demonstrated that ubiquitin-conjugating enzyme E2 L3 (UBE2L3) mediates the progression of many human cancers. However, the roles and molecular mechanisms of UBE2L3 in invasion and metastasis of lung adenocarcinoma (LUAD) are yet to be fully understood. Here, we studied the expression pattern of UBE2L3 and demonstrated that it is dramatically up-regulated in LUAD tissues compared with the normal tissues, and its overexpression is positively correlated with lymph node metastasis. Moreover, the upregulation of UBEE2L3 in LUAD tissues is associated with shorter overall survival (OS). UBE2L3 silencing impairs the metastatic capacity of LUAD cells and , while its overexpression confers an opposite effect. In addition, our data showed that UBE2L3 promotes cancer cells epithelial-mesenchymal transition (EMT) and metastasis via the glycogen synthase kinase 3β (GSK-3β)/Snail axis. Besides, UBE2L3 was shown to promote ubiquitination and degradation of the GSK-3β. Immunohistochemical analysis demonstrated that UBE2L3 expression is positively correlated with Snail, but negatively correlated with GSK-3β and E-cadherin in LUAD tissues. Taken together, our findings demonstrated that UBE2L3 modulates metastasis of LUAD cells.
肺癌是癌症相关死亡的主要原因，且死亡大多归因于远处转移。先前的研究表明，泛素结合酶E2 L3（UBE2L3）介导多种人类癌症的进展。然而，UBE2L3在肺腺癌（LUAD）侵袭和转移中的作用及分子机制尚未完全明确。在此，我们研究了UBE2L3的表达模式，发现与正常组织相比，它在LUAD组织中显著上调，且其过表达与淋巴结转移呈正相关。此外，LUAD组织中UBE2L3的上调与总生存期（OS）缩短有关。沉默UBE2L3会损害LUAD细胞的转移能力，而其过表达则产生相反的效果。另外，我们的数据表明，UBE2L3通过糖原合酶激酶3β（GSK-3β）/Snail轴促进癌细胞上皮-间质转化（EMT）和转移。此外，UBE2L3还能促进GSK-3β的泛素化和降解。免疫组化分析表明，在LUAD组织中，UBE2L3的表达与Snail呈正相关，但与GSK-3β和E-钙黏蛋白呈负相关。综上所述，我们的研究结果表明UBE2L3可调节LUAD细胞的转移。
