title: microRNA-182 targets special AT-rich sequence-binding protein 2 to promote colorectal cancer proliferation and metastasis.
abstract: BACKGROUND
  Increasing evidence has revealed that microRNAs (miRNA) played a pivotal role in regulating cancer cell proliferation and metastasis. The deregulation of miR-182 has been identified in colorectal cancer (CRC). However, the role and mechanism of miR-182 in CRC have not been completely understood yet.
  
  
  METHODS
  The expression levels of miR-182 in CRC tissues and CRC cell lines were examined by performing stem-loop quantitative RT-PCR. The stable over-expression miR-182 cell lines and control cell lines were constructed by lentivirus infection. Subsequently, CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models were performed to detect the biological functions of miR-182 in vitro and in vivo. A luciferase reporter assay was conducted to confirm target associations. Western blot and immunohistochemical analysis were performed to examine the expression changes of molecular markers that are regulated by miR-182.
  
  
  RESULTS
  We found that miR-182 expression is increased in CRC cells that originated from metastatic foci and human primary CRC tissues with lymph node metastases. The ectopic expression of miR-182 enhanced cell proliferation, invasion, and migration in vitro. Stable overexpression of miR-182 also facilitated tumor growth and metastasis in vivo too. Further research showed that miR-182 could directly target the 3'untranslated region (3'UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2, which we identified in previous studies as a CRC metastasis-associated protein. Restoring SATB2 expression could reverse the effects of miR-182 on CRC cell proliferation and migration. Investigations of possible mechanisms underlying these behaviors induced by miR-182 revealed that miR-182 induced epithelial-mesenchymal transition (EMT) by modulating the expression of key cellular molecules in EMT.
  
  
  CONCLUSIONS
  Our results illustrated that the up-regulation of miR-182 played a pivotal role in CRC tumorigenesis and metastasis, which suggesting a potential implication of miR-182 in the molecular therapy for CRC.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: Yu
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Jiang
authors.forename: Wen-Lu
authors.initials: WL
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. shuangw@126.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C521297:SATB2 protein, human; D014157:Transcription Factors