Du Wenqi, Liu Zongxiang, Zhu Wentao, Li Tongtong, Zhu Zhiman, Wei Lulu, Song Jun, Pei Dongsheng
Department of Pathology, Xuzhou Medical University, Xuzhou 221004, China.
Department of Anatomy, Xuzhou Medical University, Xuzhou 221004, China.
Cancer Biol Med. 2019 Aug;16(3):514-529. doi: 10.20892/j.issn.2095-3941.2018.0410.
CSN6 is a vital subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), which is responsible for development disorders and promotes ubiquitin-26S proteasome-dependent degradation and . Its role in the tumor development of gastric cancer remains unclear. In this study, we investigated the role of CSN6 in gastric cancer progression.
Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer. The cell proliferation was measured by CCK-8 and the EdU incorporation method. Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16. Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation. BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth .
CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival. Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation. Moreover, CSN6 interacted with p16 and a proteasome activator REGγ (PA28γ), thereby facilitating ubiquitin-independent degradation of p16.
CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16.
CSN6是组成型光形态建成9（COP9）信号体（CSN）的一个重要亚基，其与发育障碍相关，并促进泛素-26S蛋白酶体依赖性降解。其在胃癌肿瘤发生中的作用尚不清楚。在本研究中，我们探究了CSN在胃癌进展中的作用。
收集人胃癌样本并进行免疫组织化学分析以确定CSN6在胃癌中的作用。通过CCK-8和EdU掺入法检测细胞增殖。采用免疫荧光定位和免疫共沉淀研究来显示蛋白CSN6与p16之间的相互作用。进行泛素化分析以验证泛素化是否参与CSN6介导的p16降解。使用BALB/c裸鼠建立肿瘤模型以测试CSN6对癌症生长的影响。
与配对的相邻非肿瘤组织相比，胃癌组织中CSN6表达显著增加，且CSN6与较差的总生存期和疾病特异性生存期相关。此外，我们还发现CSN6下调p16蛋白表达，从而促进胃癌细胞生长和增殖。此外，CSN6与p16和蛋白酶体激活剂REGγ（PA28γ）相互作用，从而促进p16的非泛素依赖性降解。
CSN6促进p16介导的肿瘤进展丧失，并在调节p16的非泛素依赖性蛋白酶体降解中起重要作用。
