title: Roles of MicroRNA21 and MicroRNA29a in Regulating Cell Adhesion Related Genes in Bone Metastasis Secondary to Prostate Cancer.
abstract: BACKGROUND
  There is an increasing concern in the role of microRNA (miRNA) in the pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this exploratory study, we hypothesized that the expression of vinculin (VCL) and chemokine X3C ligand 1 (CX3CL1) might be downregulated in clinical samples, most likely due to the posttranscriptional modification by microRNAs. Targeted genes would be upregulated upon transfection of the bone metastatic prostate cancer cell line, PC3, with specific microRNA inhibitors.
  
  
  METHODS
  MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1. Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed paraffin embedded (FFPE) specimens were analysed. From the bone scan results, high grade CaP samples were further classified into CaP with no BM and CaP with BM. Transient transfection with respective microRNA inhibitors was done in both RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and transfected cell lines to measure VCL and CX3CL1 levels.
  
  
  RESULTS
  QPCR confirmed that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was upregulated in all FFPE specimens. Transient transfection with microRNA inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL mRNA was significantly up regulated while CX3CL1 mRNA was significantly downregulated compared to the RWPE1 case.
  
  
  CONCLUSIONS
  The downregulation of VCL in FFPE specimens is most likely regulated by miR21 based on the in vitro evidence but the exact mechanism of how miR21 can regulate VCL is unclear. Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA screening is required to understand the regulation of this chemokine in CaP with bone metastasis. Understanding miRNAmRNA interactions may provide additional knowledge for individualized study of cancers.
authors: Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Ya'acob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia Email : norfilza@ppukm.ukm.edu.my, hazlina@medic.ukm.my.
authors: Maisarah
authors: M
authors: Mohamad
authors: Norhazlina Abdul
authors: NA
authors: Wahab
authors: Rosna
authors: R
authors: Yunus
authors: Nor Azian Abdul
authors: NA
authors: Murad
authors: Zulkifli Md
authors: ZM
authors: Zainuddin
authors: Murali
authors: M
authors: Sundaram
authors: Norfilza Mohd
authors: NM
authors: Mokhtar
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection / Q000379:methods; D015854:Up-Regulation / Q000235:genetics
chemical_list: C524940:MIRN21 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger