Li Pei-Hua, Wang Lin, Pan Yao-Jie, Sang Miao-Miao, Zheng Jun-Nian, Pei Dong-Sheng
Department of Otorhinolaryngology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China.
Oncol Lett. 2018 Apr;15(4):5137-5142. doi: 10.3892/ol.2018.7963. Epub 2018 Feb 6.
c-Jun activation domain-binding protein-1 (Jab1) is a multifunctional protein involved in cell proliferation and apoptosis, DNA damage and repair and genome stability. In a number of types of human carcinoma, the abnormal expression of Jab1 is associated with poor prognosis, suggesting that Jab1 serves a vital function in tumorigenesis. However, the functional effects and the underlying molecular mechanisms of Jab1 in laryngeal squamous cell carcinoma (LSCC) progression remain poorly understood. The results of the present study demonstrate that downregulating Jab1 expression promotes LSCC apoptosis while inhibiting the proliferation of LSCC cells. Furthermore, Jab1 inhibition results in decreased protein kinase B phosphorylation accompanied by increased caspase-3 cleavage and p53 expression. It has been identified that the increased expression of Jab1 is markedly associated with LSCC progression, therefore Jab1 may be used as a novel target for the treatment of laryngeal cancer.
c-Jun激活域结合蛋白1(Jab1)是一种多功能蛋白,参与细胞增殖与凋亡、DNA损伤与修复以及基因组稳定性。在多种人类癌症中,Jab1的异常表达与预后不良相关,提示Jab1在肿瘤发生中发挥重要作用。然而,Jab1在喉鳞状细胞癌(LSCC)进展中的功能作用及潜在分子机制仍知之甚少。本研究结果表明,下调Jab1表达可促进LSCC细胞凋亡,同时抑制LSCC细胞增殖。此外,抑制Jab1会导致蛋白激酶B磷酸化减少,同时伴有半胱天冬酶-3裂解增加和p53表达增加。已确定Jab1表达增加与LSCC进展显著相关,因此Jab1可作为喉癌治疗的新靶点。