The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth

J Thorac Oncol. 2011 Dec;6(12):1984-92. doi: 10.1097/JTO.0b013e3182307eac.

Abstract

Introduction: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Animals
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / chemistry
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation
  • Female
  • Fibroblasts
  • Gene Expression
  • Humans
  • In Situ Hybridization
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • NIH 3T3 Cells
  • Neoplasm Metastasis
  • Prognosis
  • Proportional Hazards Models
  • RNA Interference
  • RNA, Long Noncoding
  • RNA, Untranslated / analysis*
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / physiology

Substances

  • Biomarkers, Tumor
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • RNA, Untranslated