title: Novel evidence for an oncogenic role of microRNA-21 in colitis-associated colorectal cancer.
abstract: miR-21 was found to be overexpressed in the colon tissues and serum of patients with UC and colorectal cancer (CRC); however, the exact roles of miR-21 in colitis-associated CRC remain unclear. The aim of our study was to investigate the biological mechanisms of miR-21 in colitis-associated colon cancer (CAC).
  
  
  
  miR-21 expression was examined in the tumours of 62 patients with CRC from China and 37 colitis-associated neoplastic tissues from Japan and Austria. The biological functions of miR-21 were studied using a series of in vitro, in vivo and clinical approaches.
  
  
  
  miR-21 levels were markedly upregulated in the tumours of 62 patients with CRC, 22 patients with CAC, and in a mouse model of CAC. Following azoxymethane and dextran sulfate sodium intervention, miR-21-knockout mice showed reduced expression of proinflammatory and procarcinogenic cytokines (interleukin (IL) 6, IL-23, IL-17A and IL-21) and a decrease in the size and number of tumours compared with the control mouse group. The absence of miR-21 resulted in the reduced expression of Ki67 and the attenuated proliferation of tumour cells with a simultaneous increase in E-cadherin and decrease in β-catenin and SOX9 in the tumours of CAC mice. Furthermore, the absence of miR-21 increased the expression of its target gene PDCD4 and subsequently modulated nuclear factor (NF)-κB activation. Meanwhile, miR-21 loss reduced STAT3 and Bcl-2 activation, causing an increase in the apoptosis of tumour cells in CAC mice.
  
  
  
  These observations provide novel evidence for miR-21 blockade to be a key strategy in reducing CAC.
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Chenzhang
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Huazhong
authors.initials: H
authors.lastname: Han
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Renyuan
authors.initials: R
authors.lastname: Gao
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine 4, Medical University Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gasche
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Huanlong
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Gastrointestinal Cancer Research Laboratory, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D003092:Colitis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016601:RNA-Binding Proteins / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D015820:Cadherins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D051176:beta Catenin
keywords: CANCER; COLORECTAL CANCER