title: MicroRNA-29b is a Novel Prognostic Marker in Colorectal Cancer.
abstract: OBJECTIVE
  Recent studies have suggested that microRNA-29 (miR-29) family members may play important roles in human cancer by regulating cell proliferation, differentiation, apoptosis, migration, and invasion. The present study aimed to investigate the clinical significance and biological function of miR-29b in colorectal cancer (CRC).
  
  
  METHODS
  Real-time polymerase chain reaction was used to quantify miR-29b expression. The association between miR-29b and survival was evaluated in 245 patients with CRC. We transfected an miR-29b mimetic into CRC cells to explore the functional role of miR-29b in vitro, based on a proliferation assay, flow cytometry, and Western blotting.
  
  
  RESULTS
  In clinical samples of CRC, miR-29b expression was significantly reduced in tumor tissues compared with normal mucosa (p < 0.012). Multivariate survival analyses indicated that miR-29b expression was an independent prognostic factor for disease-free survival (p = 0.026), lymph node metastasis (p = 0.004), and pathological T classification (p = 0.002). In a multivariate analysis of 5-year overall survival, we found a similar association between lymph node metastasis, pathological T classification, venous invasion, and miR-29b expression (p = 0.013). In vitro, low Ki-67-positive staining showed that administration of the mimic-miR-29b reduced proliferation of CRC cells. An Annexin V apoptosis assay and flow cytometric analysis revealed that miR-29b induced apoptosis and arrested the cell cycle at the G1/S transition. Moreover, miR-29b inhibited the expression of MCL1 and CDK6.
  
  
  CONCLUSIONS
  Our findings indicated that miR-29b may be a useful, novel, prognostic marker and may play important roles in regulating apoptosis and cell cycle in CRC.
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan. hyamamoto@gesurg.med.osaka-u.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Surgery, Osaka Rosai Hospital, Osaka, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ikenaga
authors.affiliation: Department of Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Surgery, Suita Municipal Hospital, Osaka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics*; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger