title: MicroRNA-211 expression promotes colorectal cancer cell growth in vitro and in vivo by targeting tumor suppressor CHD5.
abstract: BACKGROUND
  Chromodomain-helicase-DNA-binding protein 5 (CHD5) is a newly identified tumor suppressor that is frequently downregulated in a variety of human cancers. Our previous work revealed that the low expression of CHD5 in colorectal cancer is correlated with CHD5 promoter CpG island hypermethylation. In this study, we investigated the effect of microRNA-211 (miR-211)-regulated CHD5 expression on colorectal tumorigenesis.
  
  
  RESULTS
  miR-211 was predicted to target CHD5 by TargetScan software analysis. A stably expressing exogenous miR-211 colorectal cancer cell line (HCT-116(miR-211)) was generated using lentiviral transduction and used as a model for in vitro and in vivo studies. The expression level of miR-211 in HCT-116(miR-211) cells was upregulated by 16-fold compared to vector control cells (HCT-116(vector)). Exogenous miR-211 directly binds to the 3'-untranslated region (3'-UTR) of CHD5 mRNA, resulting in a 50% decrease in CHD5 protein level in HCT-116(miR-211) cells. The levels of cell proliferation, tumor growth, and cell migration of HCT-116(miR-211) cells were significantly higher than HCT-116(vector) cells under both in vitro and in vivo conditions, as determined using the methods of MTT, colony formation, flow cytometry, scratch assay, and tumor xenografts, respectively. In addition, we found that enforced expression of miR-211 in HCT-116 cells was able to alter p53 pathway-associated regulatory proteins, such as MDM2, Bcl-2, Bcl-xL, and Bax.
  
  
  CONCLUSIONS
  Our results demonstrate that CHD5 is a direct target of miR-211 regulation. Enforced expression of miR-211 promotes tumor cell growth at least in part by downregulating the expression level of the CHD5 tumor suppressor. Our results provide a better understanding of the association of between miR-211-regulated CHD5 expression and CHD5 function in colorectal tumorigenesis.
authors.affiliation: Department of Gastroenterology, Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Cai
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Pang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xinbin
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C549405:MIRN211 microRNA, human; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004265:DNA Helicases; C471926:CHD5 protein, human