title: miRNA-503 Promotes Tumor Progression and Is Associated with Early Recurrence and Poor Prognosis in Human Colorectal Cancer.
abstract: OBJECTIVE
  MicroRNA (miR)-503 is downregulated in several cancers and plays a tumor-suppressive role in carcinogenesis. However, the miR-503 expression pattern, its clinical significance and its molecular mechanism in colorectal cancer (CRC) have not been investigated.
  
  
  METHODS
  We analyzed miR-503 expression in normal mucosa (n = 20), adenoma (n = 27) and CRC (n = 20). We quantified miR-503 expression in an independent cohort (n = 191) and investigated the clinical significance of miR-503 in CRC. CRC cell lines were transfected with anti-miR-503 to assess its function and target gene.
  
  
  RESULTS
  miR-503 expression increased according to the adenoma-carcinoma sequence. High miR-503 expression was significantly associated with large tumor size, serosal invasion, lymphatic and venous invasion as well as lymph node metastasis. CRC patients with high miR-503 expression had significantly earlier relapse and poorer prognosis than those with low expression. miR-503 was an independent recurrence marker in stage I/II CRC. In vitro, attenuated miR-503 expression resulted in inhibition of proliferation, invasion and migration and acquisition of anoikis of CRC cells. The putative target gene (calcium-sensing receptor) was significantly upregulated after miR-503 attenuation.
  
  
  CONCLUSIONS
  miR-503 acts as an 'onco-miR' in CRC. High miR-503 expression is associated with early recurrence and poor prognosis in CRC.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Graduate School of Medicine, Mie University, Tsu, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Noguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Takahito
authors.initials: T
authors.lastname: Kitajima
authors.forename: Hiroki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Shusuke
authors.initials: S
authors.lastname: Toden
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000368:Aged; D023102:Anoikis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C545473:MIRN503 microRNA, human; D035683:MicroRNAs