title: The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth.
abstract: BACKGROUND
  The functions of large noncoding RNAs (ncRNAs) have remained elusive in many cases. Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types.
  
  
  METHODS
  Overexpression and RNA interference (RNAi) approaches were used for the analysis of the biological functions of MALAT-1 RNA. Tumor growth was studied in nude mice. For prognostic analysis, MALAT-1 RNA was detected on paraffin-embedded non-small cell lung cancer (NSCLC) tissue probes (n = 352) using in situ hybridization.
  
  
  RESULTS
  MALAT-1 was highly expressed in several human NSCLC cell lines. MALAT-1 expression was regulated by an endogenous negative feedback loop. In A549 NSCLCs, RNAi-mediated suppression of MALAT-1 RNA suppressed migration and clonogenic growth. Forced expression of MALAT-1 in NIH 3T3 cells significantly increased migration. Upon injection into nude mice, NSCLC xenografts with decreased MALAT-1 expression were impaired in tumor formation and growth. In situ hybridization on paraffin-embedded lung cancer tissue probes revealed that high MALAT-1 RNA expression in squamous cell carcinoma of the lung was associated with a poor prognosis. On genetic level, MALAT-1 displays the strongest association with genes involved in cancer like cellular growth, movement, proliferation, signaling, and immune regulation.
  
  
  CONCLUSIONS
  These data indicate that MALAT-1 expression levels are associated with patient survival and identify tumor-promoting functions of MALAT-1.
authors.affiliation: Department of Medicine A, Hematology, Oncology and Pulmonary Medicine, University Hospital Muenster, Muenster, Germany.
authors.forename: Lars Henning
authors.initials: LH
authors.lastname: Schmidt
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.forename: Sonja
authors.initials: S
authors.lastname: Schäffers
authors.forename: Julia
authors.initials: J
authors.lastname: Humberg
authors.forename: Dominik
authors.initials: D
authors.lastname: Jungen
authors.forename: Etmar
authors.initials: E
authors.lastname: Bulk
authors.forename: Antje
authors.initials: A
authors.lastname: Hascher
authors.forename: Danielle
authors.initials: D
authors.lastname: Wittmer
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marra
authors.forename: Ludger
authors.initials: L
authors.lastname: Hillejan
authors.forename: Karsten
authors.initials: K
authors.lastname: Wiebe
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.forename: Rainer
authors.initials: R
authors.lastname: Wiewrodt
authors.forename: Carsten
authors.initials: C
authors.lastname: Muller-Tidow
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000032:analysis* / Q000235:genetics* / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated