title: miR-124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway.
abstract: BACKGROUND
  PACE4 plays an important role in prostate cancer (PCa) proliferation and aggression, which might provide a useful target against prostate cancer. In this study, we had strived to find some key miRNAs to decrease malignancy and invasiveness of PCa through regulating PACE4 expression.
  
  
  METHODS
  Clinically pathological analysis of immunohistochemistry/in situ hybridization was carried out to detect the relationship between PACE4 expression/miRNAs and the malignancy of prostate mass. Prostate cell lines (DU145, C4-2, and BPH-1) were cultured for growth curve, immunocytochemistry analysis, colony formation, Matrigel invasion, and transcriptional/translational expression assay of PACE4-related signaling molecules for confirming the relationship. MiRNAs targeting PACE4 were predicted, validated and further-corroborated using bio-software, real-time PCR, luciferase reporter assay and transfection of miRNA mimics and inhibitor.
  
  
  RESULTS
  It was suggested that PACE4 might reflect the pathological malignancy of prostate lesion from pathology analysis. Moreover, DU145 cells, the highest PACE4-level and related TF expression indicated of the strongest malignancy and invasiveness. It was significantly found that miR-124 was presented with the biggest odd to target PACE4-3'UTR, the capability of decreasing PACE expression and slowing down cell growth and cell invasion.
  
  
  CONCLUSIONS
  It was clear that PACE4 level was closely associated with malignancy and invasiveness of PCa in vivo or in vitro MiR-124, played a crucial role inhibiting PACE4 transcription thus exhibiting obvious effects of antiproliferation and antiaggression of PCa.
authors.affiliation: Department of Urinary Surgery, Hebei United University Affiliated Hospital, Tangshan, Hebei, China.
authors.forename: Shaosan
authors.initials: S
authors.lastname: Kang
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kaimeng
authors.initials: K
authors.lastname: Hu
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Anliang
authors.initials: A
authors.lastname: Yao
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Fenghong
authors.initials: F
authors.lastname: Cao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D002478:Cells, Cultured; D045683:Furin / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D043484:Proprotein Convertases / Q000235:genetics / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; C080654:PCSK6 protein, human; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D045683:Furin
keywords: furin; invasiveness; malignancy; tumor progress