期刊
AGING-US
卷 14, 期 19, 页码 8032-8045出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.204333
关键词
bladder cancer; signal transducer and activator of transcription 3; sentrin/SUMO-specific protease 3; SUMOylation; pyrroline-5-carboxylate reductase 1; epithelial mesenchymal transformation
资金
- Hunan Provincial Health Commission Project [20200044]
- Project of Hunan Provincial Department of Education [20C1174]
- Changsha Municipal Natural Science Foundation [kq2014096]
Abnormal activation of STAT3 has been found in bladder cancer, and in our study, we discovered that SENP3 is highly expressed and regulates the activation of STAT3 through deSUMOylation. Further investigation revealed that nuclear STAT3 acts as a transcriptional factor, promoting the expression of PYCR1 gene and protein by interacting with its promoter. Silencing of PYCR1 inhibited epithelial to mesenchymal transition and mitigated the carcinogenic effects of STAT3 in bladder cancer.
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.
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