Oncotarget

Research Papers:

MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/β-catenin signaling

Han Guan, Chunhui Liu, Fang Fang, Yeqing Huang, Tao Tao, Zhixin Ling, Zonghao You, Xu Han, Shuqiu Chen, Bin Xu and Ming Chen _

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Oncotarget. 2017; 8:14693-14707. https://doi.org/10.18632/oncotarget.14711

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Abstract

Han Guan1,2,*, Chunhui Liu1,2,*, Fang Fang3,*, Yeqing Huang1,2,*, Tao Tao1,2, Zhixin Ling1,2, Zonghao You1,2, Xu Han1,2, Shuqiu Chen1,2, Bin Xu1,2, Ming Chen1,2

1Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China

2Surgical Research Center, Institute of Urology, Medical School, Nanjing, China

3Department of Immunology, Bengbu Medical College, Bengbu, China

*These authors contributed equally to this work

Correspondence to:

Bin Xu, email: [email protected]

Ming Chen, email: [email protected]

Keywords: miR-744, prostate cancer, Wnt/β-catenin signaling, NKD1, tumorigenesis

Received: October 21, 2016     Accepted: January 09, 2017     Published: January 18, 2017

ABSTRACT

Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients. In vitro studies revealed that miR-744 promotes PCa cells proliferation, enhances migration, invasion; in vivo results demonstrated that silencing of miR-744 mediated by shRNA dramatically reduces PCa xenograft tumor growth. Importantly, through human gene expression array, pathway enrichment analysis and Western blot, we identified that miR-744 dramatically activated Wnt/β-catenin pathway by targeting multiple negative regulators of Wnt/β-catenin signaling, including SFRP1, GSK3β, TLE3 and NKD1. At molecular level, we further defined that NKD1 is a major functional target of miR-744. Our findings indicate that miR-744 acts as one of oncogenic factor in the progression of CRPC by recruiting a mechanism of aberrant activation of Wnt/β-catenin signaling.


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