title: MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma.
abstract: BACKGROUND
  The molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown.
  
  
  METHODS
  The expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt.
  
  
  RESULTS
  We found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124.
  
  
  CONCLUSIONS
  Our results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Peng
authors.forename: Hao Ran
authors.initials: HR
authors.lastname: Huang
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.forename: Xiong
authors.initials: X
authors.lastname: Liu
authors.forename: Fei Peng
authors.initials: FP
authors.lastname: Zhao
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Shao Xiong
authors.initials: SX
authors.lastname: Lin
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Huai Hong
authors.initials: HH
authors.lastname: Chen
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China. li321162@qq.com.
authors.forename: Xiang Ping
authors.initials: XP
authors.lastname: Li
mesh_terms: D000328:Adult; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental
chemical_list: C484579:FOXQ1 protein, human; D051858:Forkhead Transcription Factors; C509207:MIRN124 microRNA, human; D035683:MicroRNAs
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