title: p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma.
abstract: Prostatic small cell neuroendocrine carcinoma (SCNC) is a rare but aggressive form of prostate cancer that is negative for androgen receptor (AR) and not responsive to hormonal therapy. The molecular etiology of this prostate cancer variant is not well understood; however, mutation of the p53 (TP53) tumor suppressor in prostate neuroendocrine cells inactivates the IL8-CXCR2-p53 pathway that normally inhibits cellular proliferation, leading to the development of SCNC. SCNC also overexpresses Aurora kinase A (AURKA) which is considered to be a viable therapeutic target. Therefore, the relationship of these two molecular events was studied, and we show that p53 mutation leads to increased expression of miR-25 and downregulation of the E3 ubiquitin ligase FBXW7, resulting in elevated levels of Aurora kinase A. This study demonstrates an intracellular pathway by which p53 mutation leads to Aurora kinase A expression, which is critically important for the rapid proliferation and aggressive behavior of prostatic SCNC.
  
  
  CONCLUSIONS
  The pathogenesis of prostatic SCNC involves a p53 and Aurora Kinase A signaling mechanism, both potentially targetable pathways.
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California. JiaotiHuang@mednet.ucla.edu Yin_Sun@URMC.Rochester.edu.
authors.forename: Yin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California.
authors.forename: Jill
authors.initials: J
authors.lastname: Squires
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California.
authors.forename: Behdokht
authors.initials: B
authors.lastname: Nowroozizadeh
authors.affiliation: Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Chaozhao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pathology and Urology, Jonsson Comprehensive Cancer Center and Broad Center of Regenerative Medicine and Stem Cell Research, UCLA David Geffen School of Medicine, Los Angeles, California. JiaotiHuang@mednet.ucla.edu Yin_Sun@URMC.Rochester.edu.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
mesh_terms: D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; C576917:AURKA protein, human; D064096:Aurora Kinase A