title: Down-regulation of miR-138 promotes colorectal cancer metastasis via directly targeting TWIST2.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the most common digestive system malignancy. The molecular events involved in the development and progression of CRC remain unclear. Recently, more and more evidences have showed that deregulated miRNAs participate in colorectal carcinogenesis.
  
  
  METHODS
  The expression levels of miR-138 were first examined in CRC cell lines and tumor tissues by real-time PCR. The in vitro and in vivo functional effects of miR-138 were examined further. Luciferase reporter assays were conducted to confirm the targeting associations. Kaplan-Meier analysis and log-rank tests were performed to estimate the overall survival and disease free survival rate.
  
  
  RESULTS
  miR-138 was found to be down-regulated in human colorectal cancer tissues and cell lines. Ectopic expression of miR-138 resulted in a dramatic inhibition of CRC migration and invasion in vitro and in vivo. Twist basic helix-loop-helix transcription factor 2 gene (TWIST2) was identified as one of the functional target. Restoration of miR-138 resulted in a dramatic reduction of the expression of TWIST2 at both mRNA and protein levels by directly targeting its 3'-untranslated region (3'UTR). Up-regulation of TWIST2 was detected in CRC tumors compared with adjacent normal tissues (P < 0.001) and is inversely correlated with miR-138 expression. We also identified that down-regulation of miR-138 was associated with lymph node metastasis, distant metastasis, and always predicted poor prognosis.
  
  
  CONCLUSIONS
  These data highlight a pivotal role for miR-138 in the regulation of CRC metastasis by targeting TWIST2, and suggest a potential application of miR-138 in prognosis prediction and CRC treatment.
authors.affiliation: Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China. hjr_198@hotmail.com.
authors.forename: Limin
authors.initials: L
authors.lastname: Long
authors.forename: Guoqing
authors.initials: G
authors.lastname: Huang
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhu
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Guo
authors.forename: Youshuo
authors.initials: Y
authors.lastname: Liu
authors.forename: Jirong
authors.initials: J
authors.lastname: Huo
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011379:Prognosis; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1