title: A Feed-Forward Regulatory Loop between HuR and the Long Noncoding RNA HOTAIR Promotes Head and Neck Squamous Cell Carcinoma Progression and Metastasis.
abstract: OBJECTIVE
  The lncRNA Homeobox (HOX) transcript antisense RNA (HOTAIR) is overexpressed in numerous cancers. HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes. However, whether HOTAIR is regulated and the mechanisms by which it affects head and neck squamous cell carcinoma (HNSCC) are not well understood.
  
  
  METHODS
  MTT, cell cycle arrest and apoptotic assays were used to examine the effects of HOTAIR and HuR on cell viability in SCC25 and FaDu cells. Wound healing and transwell invasion analysis were performed to detect the effects of HOTAIR and HuR on cell migration and invasion. The interaction between HuR and HOTAIR was confirmed via qRT-PCR, western blots, luciferase reporter and RIP assays. Finally, qRT-PCR analysis was used to detect the levels of HuR and HOTAIR in HNSCC tumours and adjacent normal tissues.
  
  
  RESULTS
  Knockdown of HOTAIR and HuR decreased cell viability, cellular migration and invasion. Moreover, HuR interacted and stabilized HOTAIR stability and thus promoted HOTAIR expression. Notably, HOTAIR acted as a miRNA sponge for HuR. HuR also reinforced HOTAIR sponge activity through miRNA recruitment, thus enhancing HuR expression in turn. Finally, HuR and HOTAIR levels were positively correlated and significantly up-regulated in tumours samples.
  
  
  CONCLUSIONS
  We demonstrated the existence of a regulatory loop in which the expression of HOTAIR and HuR is reciprocally and temporally regulated during the metastasis and progression of HNSCC.
authors.affiliation: Department of Otolaryngology- Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cheng-Zhi
authors.initials: CZ
authors.lastname: Xu
authors.forename: Chenyan
authors.initials: C
authors.lastname: Jiang
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Wu
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yan
authors.forename: Runjie
authors.initials: R
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011485:Protein Binding; D020871:RNA Stability / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000067780:ELAV-Like Protein 1; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C561566:HOTAIR long untranslated RNA, human; C549242:MIRN7-1 microRNA, human