The incidence of lung diseases and cancer caused by cigarette smoke is increasing. The molecular mechanism(s) of gene regulation induced by cigarette smoke that ultimately lead to cancer remains unclear. This report describes a novel long non-coding 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. Researchers at the University of California, Davis, School of Medicine have termed this lncRNA, SCAL1 (Smoke and Cancer Associated LncRNA 1). This lncRNA is located in chromosome 5 and initial sequencing analysis reveals a transcript with 4 exons and three introns. Expression of SCAL1 is regulated transcriptionally by NRF2 as determined by siRNA knockdown of NRF2 and KEAP1. An NF-E2 motif is identified in the promoter region that shows binding to NRF2 following its activation. Functionally, siRNA knockdown of SCAL1 in HBE1 cells shows significant potentiation of cytotoxicity induced by CSE in vitro. Altogether, these results identify a novel and intriguing new non-coding RNA that may act downstream of NRF2 to regulate gene expression and mediate oxidative stress protection in airway epithelial cells.
- Thai P, Statt S, Chen CH, Liang E, Campbell C, Wu R. (2013) Characterization of a Novel Long Non-Coding RNA, SCAL1, Induced by Cigarette Smoke and Elevated in Lung Cancer Cell Lines. Am J Respir Cell Mol Biol [Epub ahead of print]. [abstract]