Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.
Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.
复制标题
DOI：
10.1186/s11658-023-00465-6
复制
发表时间：
2023-07-31
影响因子：
8.3
通讯作者：
中科院分区：
文献类型：
--
作者：
膀胱癌（BLCA）是一种经常转移并导致患者预后不良的恶性肿瘤。了解 BLCA 进展和转移的分子机制并识别潜在的生物标志物至关重要。使用定量 PCR、免疫印迹和免疫组织化学分析方法分析肽酶抑制剂 16 (PI16) 的表达。使用伤口愈合、Transwell、人脐静脉内皮细胞管形成测定以及体内肿瘤模型评估 PI16 的功能作用。使用荧光素酶报告基因系统、免疫印迹和免疫荧光测定检查 PI16 对核因子 κB (NF-κB) 信号激活的影响。使用免疫共沉淀研究 PI16 与膜联蛋白-A1 (ANXA1) 和 NEMO 的相互作用。 PI16 表达在膀胱癌组织中下调，较低的 PI16 水平与 BLCA 患者的疾病进展和较差的生存率相关。过表达PI16会在体外和体内抑制BLCA细胞的生长、运动、侵袭和血管生成，而沉默PI16则会产生相反的效果。从机制上讲，PI16通过与ANXA1相互作用抑制NF-κB通路的激活，从而抑制NEMO的K63和M1泛素化。这些结果表明，PI16 通过抑制肿瘤生长和转移，在 BLCA 中发挥肿瘤抑制因子的作用。此外，PI16 可以作为转移性 BLCA 的潜在生物标志物。在线版本包含可在 10.1186/s11658-023-00465-6 获取的补充材料。
Bladder cancer (BLCA) is a malignancy that frequently metastasizes and leads to poor patient prognosis. It is essential to understand the molecular mechanisms underlying the progression and metastasis of BLCA and identify potential biomarkers. The expression of peptidase inhibitor 16 (PI16) was analysed using quantitative PCR, immunoblotting and immunohistochemistry assays. The functional roles of PI16 were evaluated using wound healing, transwell, and human umbilical vein endothelial cell tube formation assays, as well as in vivo tumour models. The effects of PI16 on nuclear factor κB (NF-κB) signalling activation were examined using luciferase reporter gene systems, immunoblotting and immunofluorescence assays. Co-immunoprecipitation was used to investigate the interaction of PI16 with annexin-A1 (ANXA1) and NEMO. PI16 expression was downregulated in bladder cancer tissues, and lower PI16 levels correlated with disease progression and poor survival in patients with BLCA. Overexpressing PI16 inhibited BLCA cell growth, motility, invasion and angiogenesis in vitro and in vivo, while silencing PI16 had the opposite effects. Mechanistically, PI16 inhibited the activation of the NF-κB pathway by interacting with ANXA1, which inhibited K63 and M1 ubiquitination of NEMO. These results indicate that PI16 functions as a tumour suppressor in BLCA by inhibiting tumour growth and metastasis. Additionally, PI16 may serve as a potential biomarker for metastatic BLCA. The online version contains supplementary material available at 10.1186/s11658-023-00465-6.
登录
查看更多内容
前列腺分泌蛋白 94 以钙敏感方式抑制哺乳动物 CAP 蛋白 CRISP2 的甾醇结合和输出。
DOI：
10.1016/j.jbc.2022.101600
发表时间：
2022-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
El Atab O;Kocabey AE;Asojo OA;Schneiter R
通讯作者：
Schneiter R
annexin A1通过调节EGFR信号通路促进膀胱癌进展
影响因子：
5.8
作者：
Li P;Li L;Li Z;Wang S;Li R;Zhao W;Feng Y;Huang S;Li L;Qiu H;Xia S
通讯作者：
Xia S
影响因子：
8.7
作者：
Ikeda F
通讯作者：
Ikeda F
影响因子：
8.3
作者：
Feng W;Xue T;Huang S;Shi Q;Tang C;Cui G;Yang G;Gong H;Guo H
通讯作者：
Guo H
影响因子：
9
作者：
Ma JX;Yan BX;Zhang J;Jiang BH;Guo Y;Riedel H;Mueller MD;Remick SC;Yu JJ
通讯作者：
Yu JJ