Oncotarget

Research Papers:

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

Daojun Lv, Huayan Wu, Rongwei Xing, Fangpeng Shu, Bin Lei, Chengyong Lei, Xumin Zhou, Bo Wan, Yu Yang, Liren Zhong, Xiangming Mao and Yaguang Zou _

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Oncotarget. 2017; 8:13586-13599. https://doi.org/10.18632/oncotarget.14600

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Abstract

Daojun Lv1,*, Huayan Wu1,*, Rongwei Xing4,*, Fangpeng Shu1, Bin Lei1, Chengyong Lei1, Xumin Zhou1, Bo Wan1, Yu Yang2, Liren Zhong1, Xiangming Mao1,2, Yaguang Zou3

1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China

2Department of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, Guangdong Province, 518036, China

3Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, P. R. China

4Department 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: [email protected]

Yaguang Zou, email: [email protected]

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.


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