TY - JOUR T1 - CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16<sup>INK4a</sup> JF - Cancer Biology and Medicine JO - Cancer Biol Med SP - 514 LP - 529 DO - 10.20892/j.issn.2095-3941.2018.0410 VL - 16 IS - 3 AU - Wenqi Du AU - Zongxiang Liu AU - Wentao Zhu AU - Tongtong Li AU - Zhiman Zhu AU - Lulu Wei AU - Jun Song AU - Dongsheng Pei Y1 - 2019/08/01 UR - http://www.cancerbiomed.org/content/16/3/514.abstract N2 - Objective: 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 in vitro and vivo. Its role in the tumor development of gastric cancer remains unclear. In this study, we investigated the role of CSN6 in gastric cancer progression.Methods: 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 in vivo.Results: 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.Conclusions: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16. ER -