Research Papers:

MiR-4638-5p inhibits castration resistance of prostate cancer through repressing Kidins220 expression and PI3K/AKT pathway activity

Yang Wang, Ning Shao, Xueying Mao, Minmin Zhu, Weifei Fan, Zhixiang Shen, Rong Xiao, Chuncai Wang, Wenping Bao, Xinyu Xu, Chun Yang, Jian Dong, Deshui Yu, Yan Wu, Caixia Zhu, Liting Wen, Xiaojie Lu, Yong-Jie Lu and Ninghan Feng _

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Oncotarget. 2016; 7:47444-47464. https://doi.org/10.18632/oncotarget.10165

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Yang Wang1,2,*, Ning Shao1,2,*, Xueying Mao3,*, Minmin Zhu1,*, Weifei Fan4,*, Zhixiang Shen4,*, Rong Xiao5,*, Chuncai Wang5, Wenping Bao5, Xinyu Xu1, Chun Yang1, Jian Dong1, Deshui Yu1, Yan Wu1, Caixia Zhu1, Liting Wen1, Xiaojie Lu6,#, Yong-Jie Lu3,#, Ninghan Feng1,2,#

1Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China

2Wuxi Medical School, Jiangnan University, Wuxi, China

3Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom

4Jiangsu Province Geriatric Institute, Nanjing, China

5College of Clinical Medicine, Nanjing Medical University, Nanjing, China

6Centre for Translational Medicine, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China

*These authors contributed equally to this work

#These authors have equal senior contribution

Correspondence to:

Ninghan Feng, email: [email protected]

Yong-Jie Lu, email: [email protected]

Xiaojie Lu, email: [email protected]

Keywords: castration resistant prostate cancer, miR-4638-5p, Kidins220, PI3K/AKT pathway, angiogenesis

Received: April 28, 2016     Accepted: June 06, 2016     Published: June 18, 2016


MicroRNAs (miRNAs) are short, conserved segments of non-coding RNA which play a significant role in prostate cancer development and progression. To identify miRNAs associated with castration resistance, we performed miRNA microarray analysis comparing castration resistant prostate cancer (CRPC) with androgen dependent prostate cancer (ADPC). We identified common underexpression of miR-4638-5p in CRPC compared to ADPC samples, which were further confirmed by quantitative PCR analysis. The role of miR-4638-5p in prostate cancer androgen-independent growth has been demonstrated both in vitro and in vivo. We also identified Kidins220 as a target gene directly regulated by miR-4638-5p and shRNA-mediated knockdown of Kidins220 phenocopied miR-4638-5p restoration. Subsequently, we revealed that Kidins220 activates PI3K/AKT pathway, which plays a key role in CRPC. Loss of miR- 4638-5p may lead to CRPC through the activity of Kidins220 and PI3K/AKT pathway. Furthermore, we found that miR-4638-5p, through regulating Kidins220 and the downstream activity of VEGF and PI3K/AKT pathway, influences prostate cancer progression via angiogenesis. The identification of miR-4638-5p down-regulation in CRPC and the understanding of the functional role of miR-4638-5p and its downstream genes/pathways have the potential to develop biomarkers for CRPC onset and to identify novel targets for novel forms of treatments of this lethal form of PCa.

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