Effects of Holliday Junction-Recognition Protein-Mediated C-Jun N-Terminal Kinase/ Signal Transducer and Activator of Transcription 3 Signaling Pathway on Cell Proliferation, Cell Cycle and Cell Apoptosis in Bladder Urothelial Carcinoma

• Published in: The Tohoku Journal of Experimental Medicine Vol. 259; no. 3; pp. 209 - 219
• Main Authors: Gao, Song, Zhou, Xiao-Qing, Wu, Qi, Chen, Xue-Dong, Li, Peng, Qin, Ye-Min
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 2023
• Subjects: Apoptosis; bladder urothelial carcinoma; c-Jun N-terminal kinase; Carcinoma, Transitional Cell; Cell Cycle; Cell Proliferation; DNA, Cruciform; Holliday junction recognition protein; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; JNK Mitogen-Activated Protein Kinases - pharmacology; Proliferating Cell Nuclear Antigen - metabolism; Proliferating Cell Nuclear Antigen - pharmacology; Protein C - metabolism; Protein C - pharmacology; signal transducer and activator of transcription 3; Signal Transduction; signaling pathway; STAT3 Transcription Factor - metabolism; Urinary Bladder; Urinary Bladder Neoplasms; signaling pathway; c-Jun N-terminal kinase; signal transducer and activator of transcription 3; Holliday junction recognition protein; bladder urothelial carcinoma
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.2022.J113

The Holliday Junction-Recognition Protein (HJURP) was upregulated in several tumors, which was associated with poor outcome. This study investigated the effects of the HJURP-mediated c-Jun N-terminal kinase (JNK)/ signal transducer and activator of transcription 3 (STAT3) pathway on bladder urothelial carcinoma (BLUC). Online databases were used to analyze HJURP expression in BLUC and the correlation of HJURP to JNK1 [mitogen-activated protein kinase 8 (MAPK8)], JNK2 (MAPK9), STAT3, marker of proliferation Ki-67 (MKI67), proliferating cell nuclear antigen (PCNA), cyclin dependent kinase 2 (CDK2), CDK4 and CDK6. HJURP expression was detected in BLUC cells and human normal primary bladder epithelial cells (BdECs). BLUC cells were treated with HJURP lentivirus activation /shRNA lentivirus particles or JNK inhibitor SP600125. HJURP was upregulated in BLUC tissues and correlated with poor prognosis of patients (all P < 0.05). HJURP in tumor positively correlated with MAPK8 (R = 0.30), MAPK9 (R = 0.30), STAT3 (R = 0.15), MKI67 (R = 0.60), PCNA (R = 0.46), CDK2 (R = 0.39), CDK4 (R = 0.24) and CDK6 (R = 0.21). The JNK inhibitor SP600125 decreased p-JNK/JNK and p-STAT3/STAT3 in BLUC cells, which was reversed by HJURP overexpression (P < 0.05). The HJURP-mediated JNK/STAT3 pathway promoted BLUC cell proliferation and inhibited cell apoptosis (P < 0.05). HJURP reversed the arrested G0/G1 phase of BLUC cells by SP600125. HJURP acted as an oncogene to regulate BLUC cell proliferation, apoptosis and the cell cycle by mediating the JNK/STAT3 pathway. Therefore, HJURP targeting might be an attractive novel therapeutic target for early diagnosis and treatment in BLUC.