Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha City, Hunan Province 410005, China.
Aging (Albany NY). 2022 Oct 11;14(19):8032-8045. doi: 10.18632/aging.204333.
Abnormal activation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including bladder cancer (BC). In our study, we examined the regulation of STAT3 post-translational modifications (PTMs) and found that SENP3 is high in bladder cancer. Sentrin/SUMO-specific protease3 (SENP3) and STAT3 were highly expressed in BC tissues when compared with tissue adjacent to carcinoma. SENP3 induced STAT3 protein level and p-STAT3 translocating into nuclear through deSUMOylation of STAT3. Further, nuclear STAT3, as a transcriptional activity factor, promoted pyrroline-5-carboxylate reductase 1 PYCR1 gene and protein level by interacting with the promoter of (PYCR1). Next, we found that knockdown of PYCR1 inhibited Epithelial to mesenchymal transition of bladder cancer, and simultaneously mitigated the carcinogenic effects of STAT3. , STAT3 knockdown in bladder cancer cells inhibited cell proliferation, migration, and invasion. In contrast, SENP3 overexpression reversed these effects. In all, results lend novel insights into the regulation of STAT3, which has key roles in bladder cancer progression.
信号转导子和转录激活子 3（STAT3）的异常激活已在包括膀胱癌（BC）在内的各种人类癌症中被发现。在我们的研究中，我们研究了 STAT3 翻译后修饰（PTM）的调节，发现 SENP3 在膀胱癌中高表达。与癌旁组织相比，SENP3 和 STAT3 在膀胱癌组织中高表达。SENP3 通过去 SUMO 化 STAT3 诱导 STAT3 蛋白水平和 p-STAT3 向核内转位。此外，核 STAT3 作为转录活性因子，通过与（PYCR1）启动子相互作用，促进吡咯啉-5-羧酸还原酶 1（PYCR1）基因和蛋白水平。接下来，我们发现敲低 PYCR1 抑制了膀胱癌的上皮间质转化，同时减轻了 STAT3 的致癌作用。在膀胱癌细胞中敲低 STAT3 抑制了细胞增殖、迁移和侵袭。相比之下，SENP3 的过表达逆转了这些效应。总之，这些结果为 STAT3 的调节提供了新的见解，STAT3 在膀胱癌的进展中具有关键作用。
