title: MicroRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting caveolin-2 involved in focal adhesion pathway.
abstract: OBJECTIVE
  Our microRNA expression signature of renal cell carcinoma revealed that miR-218 expression was significantly decreased in cancer tissues, suggesting that miR-218 is a candidate tumor suppressor. We investigated the functional significance of miR-218 in cancer cells and identified what are to our knowledge novel miR-218 mediated cancer pathways in renal cell carcinoma.
  
  
  METHODS
  Gain of function studies using mature miR-218 were performed to investigate cell proliferation, migration and invasion in the A498 and 786-O renal cell carcinoma cell lines. To identify miR-218 mediated molecular pathways and responsible genes in renal cell carcinoma, we used gene expression and in silico database analyses. Loss of function assays were performed to investigate the functional significance of miR-218 target genes.
  
  
  RESULTS
  Restoration of mature miR-218 significantly inhibited RCC cell proliferation, migration and invasion. Gene expression studies and luciferase reporter assays showed that CAV2 involved in the focal adhesion pathway was directly regulated by miR-218. A silencing study of CAV2 revealed significant inhibition of cell proliferation, migration and invasion. CAV2 mRNA and protein expression was significantly up-regulated in renal cell carcinoma clinical specimens.
  
  
  CONCLUSIONS
  Loss of tumor suppressive miR-218 enhances cancer cell migration and invasion through dysregulation of the focal adhesion pathway, especially CAV2 as an oncogenic function in renal cell carcinoma. Tumor suppressive microRNA mediated cancer pathways and responsible genes provide new insights into the potential mechanisms of renal cell carcinoma oncogenesis and metastasis.
authors: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Takeshi
authors: T
authors: Yamasaki
authors: Naohiko
authors: N
authors: Seki
authors: Hirofumi
authors: H
authors: Yoshino
authors: Toshihiko
authors: T
authors: Itesako
authors: Hideo
authors: H
authors: Hidaka
authors: Yasutoshi
authors: Y
authors: Yamada
authors: Shuichi
authors: S
authors: Tatarano
authors: Tomokazu
authors: T
authors: Yonezawa
authors: Takashi
authors: T
authors: Kinoshita
authors: Masayuki
authors: M
authors: Nakagawa
authors: Hideki
authors: H
authors: Enokida
mesh_terms: D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D051243:Caveolin 2 / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology; D049109:Cell Proliferation; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
chemical_list: D051243:Caveolin 2; D035683:MicroRNAs
keywords: 3′UTR; 3′untranslated region; BC; CAV2; EGFR; EMT; GEO; Gene Expression Omnibus; KEGG; Kyoto Encyclopedia of Genes and Genomics; MIRN218 microRNA, human; NKT; P/N; PCR; RCC; RT-PCR; TF; bladder cancer; carcinoma, renal cell; caveolin 2; caveolin-2; epidermal growth factor receptor; epithelial-mesenchymal transition; focal adhesions; kidney; miRNA; microRNA; normal kidney tissue; part number; polymerase chain reaction; renal cell carcinoma; reverse transcriptase-PCR; transfectant