title: MiR-4638-5p inhibits castration resistance of prostate cancer through repressing Kidins220 expression and PI3K/AKT pathway activity.
abstract: 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.
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.|Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.|Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shao
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Geriatric Institute, Nanjing, China.
authors.forename: Weifei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Jiangsu Province Geriatric Institute, Nanjing, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: College of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.affiliation: College of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Chuncai
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Clinical Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Deshui
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Wen
authors.affiliation: Centre for Translational Medicine, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Lu
authors.affiliation: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.|Wuxi Medical School, Jiangnan University, Wuxi, China.
authors.forename: Ninghan
authors.initials: N
authors.lastname: Feng
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000209:etiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C482591:KIDINS220 protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Kidins220; PI3K/AKT pathway; angiogenesis; castration resistant prostate cancer; miR-4638-5p