title: Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen.
abstract: BACKGROUND
  The tumor microenvironment is a crucial determinant in tumor progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), is aberrantly enriched in the tumor microenvironment and promotes tumor progression. Long intergenic non-coding RNAs (lincRNA) are a new family of regulatory RNAs that modulate fundamental cellular processes via diverse mechanisms.
  
  
  RESULTS
  We investigated whether the expression of lincRNAs was regulated by the tumor promoting Col-1. In a three-dimensional organotypic culture model using the reconstituted basement membrane ECM Matrigel (rBM 3-D), supplementation of Col-1 disrupted acini, a differentiation feature of well-differentiated lung adenocarcinoma cells, and concurrently induced the expression of a tumor-promoting lincRNA, HOX transcript antisense RNA (HOTAIR). Induction of HOTAIR by Col-1 was diminished by a neutralizing antibody against the Col-1 receptor α2β1 integrin. Col-1 activates the expression of a reporter gene controlled by the human HOTAIR promoter. Moreover the expression of HOTAIR and Col-1 was concurrently up-regulated in human non-small cell lung cancer.
  
  
  CONCLUSIONS
  Our findings indicate that tumor-promoting Col-1 up-regulates the expression of HOTAIR in NSCLC cells. These initial results warrant further investigation of HOTAIR and other lincRNA genes in lung tumorigenesis.
authors.affiliation: Department of Medicine and Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Hong T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhuo
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Cui
authors.forename: Claire
authors.initials: C
authors.lastname: Fewell
authors.forename: Erik K
authors.initials: EK
authors.lastname: Flemington
authors.forename: Bin
authors.initials: B
authors.lastname: Shan
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment; D015854:Up-Regulation
chemical_list: D024042:Collagen Type I; C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding