Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines

Philip Thai, Sarah Statt, Ching-Hsien Chen, Ellen Liang, Caitlin Campbell, Reen Wu

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

The incidence of lung diseases and cancer caused by cigarette smoke is increasing. The molecular mechanisms of gene regulation induced by cigarette smoke that ultimately lead to cancer remain unclear. This report describes a novel long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) both in vitro and in vivo and is elevated in numerous lung cancer cell lines. We have termed this lncRNA the smoke and cancer-associated lncRNA-1 (SCAL1). This lncRNA is located in chromosome 5, and initial sequencing analysis reveals a transcript with four exonsandthree introns.Theexpression of SCAL1 is regulated transcriptionally by nuclear factor erythroid 2- related factor (NRF2), as determined by the small, interfering RNA (siRNA) knockdown of NRF2 and kelch-like ECH-associated protein 1 (KEAP1). A nuclear factor erythroid-derived 2 (NF-E2) motif was identified in the promoter region that shows binding to NRF2 after its activation. Functionally, the siRNA knockdownof SCAL1 inhuman bronchial epithelial cells shows a significant potentiation of cytotoxicity induced by CSE in vitro. Altogether, these results identify a novel and intriguing new noncoding RNA that may act downstream of NRF2 to regulate gene expression and mediate oxidative stress protection in airway epithelial cells.

Original languageEnglish (US)
Pages (from-to)204-211
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume49
Issue number2
DOIs
StatePublished - Aug 2013

Keywords

  • Cancer
  • Epigenetics
  • LincRNA
  • NRF2
  • Smoke

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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