title: Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines.
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 exons and three introns. The expression 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 knockdown of SCAL1 in human 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.
authors.affiliation: Center for Comparative Respiratory Biology and Medicine, Genome and Biomedical Science Facility, and Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, CA 95616, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Thai
authors.forename: Sarah
authors.initials: S
authors.lastname: Statt
authors.forename: Ching Hsien
authors.initials: CH
authors.lastname: Chen
authors.forename: Ellen
authors.initials: E
authors.lastname: Liang
authors.forename: Caitlin
authors.initials: C
authors.lastname: Campbell
authors.forename: Reen
authors.initials: R
authors.lastname: Wu
mesh_terms: D045744:Cell Line, Tumor; D002895:Chromosomes, Human, Pair 5 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis; D000072019:Kelch-Like ECH-Associated Protein 1; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000096:biosynthesis; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D018384:Oxidative Stress; D062085:RNA, Long Noncoding / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D050984:NF-E2 Transcription Factor, p45 Subunit; D051267:NF-E2-Related Factor 2; C494692:NFE2 protein, human; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm