title: Significance of miR-148a in Colorectal Neoplasia: Downregulation of miR-148a Contributes to the Carcinogenesis and Cell Invasion of Colorectal Cancer.
abstract: OBJECTIVE
  Colorectal cancer (CRC) develops through the deregulation of gene expression and the accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development, where they can act as oncogenes or oncosuppressors.
  
  
  METHODS
  miR-148a expression was measured by qRT-PCR in patients with colorectal adenoma (n = 21) and CRC (stage I-IV, n = 159) using formalin-fixed paraffin-embedded tissue samples. In situ hybridization (ISH) using an miR-148a-specific probe was also performed. To further confirm the direct effect of miR-148a on matrix metalloproteinase (MMP)7 expression in CRC, MTT and cell invasion assays using HT29 and WiDr cells were performed.
  
  
  RESULTS
  miR-148a expression was found to be clearly downregulated in high-grade adenoma compared to low-grade adenoma on both qRT-PCR and ISH analysis. Downregulation of miR-148a expression was significantly correlated with advanced clinicopathological features and was an independent prognostic classifier in patients with stage III CRC. In CRC cells and tissues, miR-148a expression was inversely correlated with the expression of MMP7.
  
  
  CONCLUSIONS
  We showed the collaborative participation of miR-148a and MMP7 in CRC cell invasion. These results also demonstrate that the downregulation of miR-148a expression promotes CRC progression, especially carcinogenesis and cancer cell invasion.
authors.affiliation: Department of Molecular Pathology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hibino
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Keisuke
authors.initials: K
authors.lastname: Goto
authors.forename: Htoo Zarni
authors.initials: HZ
authors.lastname: Oo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D020783:Matrix Metalloproteinase 7