HnRNP-L mediates bladder cancer progression by inhibiting apoptotic signaling and enhancing MAPK signaling pathways

Autor: Daojun Lv, Fangpeng Shu, Yu Yang, Huayan Wu, Bo Wan, Xumin Zhou, Bin Lei, Cheng-Yong Lei, Liren Zhong, Rongwei Xing, Xiangming Mao, Yaguang Zou
Rok vydání: 2016
Předmět:
0301 basic medicine
MAPK/ERK pathway
Male
Cell cycle checkpoint
MAP Kinase Signaling System
viruses
genetic processes
epithelial-mesenchymal transition
Apoptosis
environment and public health
03 medical and health sciences
0302 clinical medicine
intrinsic apoptosis
Heterogeneous-Nuclear Ribonucleoprotein L
Cell Movement
Medicine
Humans
Epithelial–mesenchymal transition
Cell Proliferation
Bladder cancer
business.industry
Intrinsic apoptosis
heterogeneous nuclear ribonucleoprotein L
Cell Cycle Checkpoints
Middle Aged
medicine.disease
MAPK
Up-Regulation
030104 developmental biology
Oncology
Urinary Bladder Neoplasms
Tumor progression
030220 oncology & carcinogenesis
Immunology
Cancer research
health occupations
Disease Progression
bladder cancer
Ectopic expression
Female
business
Signal Transduction
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Daojun Lv 1, * , Huayan Wu 1, * , Rongwei Xing 4, * , Fangpeng Shu 1 , Bin Lei 1 , Chengyong Lei 1 , Xumin Zhou 1 , Bo Wan 1 , Yu Yang 2 , Liren Zhong 1 , Xiangming Mao 1, 2 , Yaguang Zou 3 1 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China 2 Department of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong Province, 518036, China 3 Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China 4 Department of Urology, Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai 264200, P. R. China * These authors contributed equally to this work Correspondence to: Xiangming Mao, email: mxming2014@163.com Yaguang Zou, email: 18620050609@163.com Keywords: bladder cancer, heterogeneous nuclear ribonucleoprotein L, epithelial-mesenchymal transition, intrinsic apoptosis, MAPK Received: August 05, 2016 Accepted: January 03, 2017 Published: January 11, 2017 ABSTRACT Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo . Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration. All these cellular changes were reversed by ectopic expression of hnRNP-L. Deletion of hnRNP-L resulted in decreased expression of Bcl-2, enhanced expression of caspases-3, -6 and -9 and inhibition of the MAPK signaling pathway. These findings demonstrate that hnRNP-L contributes to poor prognosis and tumor progression of BC by inhibiting the intrinsic apoptotic signaling and enhancing MAPK signaling pathways.
Databáze: OpenAIRE