title: MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway.
abstract: BACKGROUND
  To date microRNAs and their contribution to the onset and propagation of salivary adenoid cystic carcinoma (SACC) are limited. The objective of this study was to identify miR-181a and its mechanism in the metastasis of SACC.
  
  
  METHODS
  At first microarray and quantitative RT-PCR were used to investigate microRNA profiles and miR-181a in paired SACC cell lines with different metastatic potential. Then the effect of miR-181a on metastatic potential of SACC was investigated. MiR-181a target genes and Snai2 promoter activity were investigated using luciferase reporter gene assays. Western blot was used to detect MAPK-Snai2 pathway-related protein level.
  
  
  RESULTS
  A panel of deregulated microRNAs (including miR-181a) was identified in paired of SACC cell lines. Functional analysis indicated that miR-181a inhibited SACC cell migration, invasion and proliferation in vitro, and it suppressed tumor growth and lung metastasis in vivo. Direct targeting of miR-181a to MAP2K1, MAPK1 and Snai2 was confirmed by luciferase reporter gene assays. MiR-181a mimic inhibited the expression of MAP2K1, MAPK1 and Snai2 in SACC cells. MAP2K1 or MAPK1 siRNA suppressed Snai2 gene promoter activity and reduced Snai2 expression and the metastatic potential of SACC cells.
  
  
  CONCLUSIONS
  Our results indicate that miR-181a plays an important role in the metastasis of SACC, and may serve as a novel therapeutic target for SACC. MiR-181a regulates the MAPK-Snai2 pathway both through direct cis-regulatory mechanism and through indirect trans-regulatory mechanism.
  
  
  CONCLUSIONS
  To our knowledge, this is the first study revealing that miR-181a deregulation mediated the metastasis of SACC by regulating MAPK-Snai2 pathway.
authors.affiliation: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: He
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Zhujian
authors.initials: Z
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Cai
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
mesh_terms: D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: GAPDH; GF; LNA; Locked nucleic acid; MAP2K; MAPK; Metastasis; MiR-181a; MicroRNA; NGF; SACC; Salivary adenoid cystic carcinoma; Snai2; TGF; VEGF; glyceraldehyde-3-phosphate dehydrogenase; growth factor; mitogen-activated protein kinase; mitogen-activated protein kinase kinase; nerve growth factor; salivary adenoid cystic carcinoma; siRNA; small interfering RNA; transforming growth factor; vascular endothelial growth factor