Open AccessLong noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small‐cell lung cancer
Author(s) -
Ono Hiroshi,
Motoi Noriko,
Nagano Hiroko,
Miyauchi Eisaku,
Ushijima Masaru,
Matsuura Masaaki,
Okumura Sakae,
Nishio Makoto,
Hirose Tetsuro,
Inase Naohiko,
Ishikawa Yuichi
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.220
Subject(s) - hotair , gene knockdown , cancer research , long non coding rna , biology , cell growth , downregulation and upregulation , rna interference , lung cancer , gene silencing , microarray analysis techniques , gene expression , cell culture , rna , gene , medicine , pathology , genetics
Small‐cell lung cancer ( SCLC ) is a subtype of lung cancer with poor prognosis. To identify accurate predictive biomarkers and effective therapeutic modalities, we focus on a long noncoding RNA , Hox transcript antisense intergenic RNA ( HOTAIR ), and investigated its expression, cellular functions, and clinical relevance in SCLC . In this study, HOTAIR expression was assessed in 35 surgical SCLC samples and 10 SCLC cell lines. The efficacy of knockdown of HOTAIR by siRNA transfection was evaluated in SBC ‐3 cells in vitro, and the gene expression was analyzed using microarray. HOTAIR was expressed highly in pure, rather than combined, SCLC ( P = 0.012), that the subgroup with high expression had significantly more pure SCLC ( P = 0.04), more lymphatic invasion ( P = 0.03) and more relapse ( P = 0.04) than the low‐expression subgroup. The knockdown of HOTAIR in SBC ‐3 cells led to decreased proliferation activity and decreased invasiveness in vitro. Gene expression analysis indicated that depletion of HOTAIR resulted in upregulation of cell adhesion‐related genes such as ASTN 1 , PCDHA 1 , and mucin production‐related genes such as MUC 5 AC , and downregulation of genes involved in neuronal growth and signal transduction including NTM and PTK 2B . Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target.