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. In vitro, 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.

中文翻译：

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SENP3通过STAT3去SUMO化影响PYCR1表达促进膀胱癌增殖和EMT转化


信号转导子和转录激活子 3 (STAT3) 的异常激活已在多种类型的人类癌症中被发现，包括膀胱癌 (BC)。在我们的研究中，我们检查了 STAT3 翻译后修饰 (PTM) 的调节，发现 SENP3 在膀胱癌中含量很高。与癌旁组织相比，Sentrin/SUMO 特异性蛋白酶 3 (SENP3) 和 STAT3 在 BC 组织中高表达。 SENP3 诱导 STAT3 蛋白水平，并通过 STAT3 的去SUMOylation 使 p-STAT3 转位到核中。此外，核STAT3作为转录活性因子，通过与(PYCR1)的启动子相互作用，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PYCR1的敲除抑制了膀胱癌的上皮细胞向间质细胞的转化，同时减轻了STAT3的致癌作用。在体外，膀胱癌细胞中 STAT3 敲低可抑制细胞增殖、迁移和侵袭。相反，SENP3 过度表达逆转了这些影响。总而言之，这些结果为 STAT3 的调节提供了新的见解，STAT3 在膀胱癌进展中发挥着关键作用。