title: Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer.
abstract: 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 ASTN1, PCDHA1, and mucin production-related genes such as MUC5AC, and downregulation of genes involved in neuronal growth and signal transduction including NTM and PTK2B. Our results suggest that HOTAIR has an oncogenic role in SCLC and could be a prognostic biomarker and therapeutic target.
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ono
authors.forename: Noriko
authors.initials: N
authors.lastname: Motoi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagano
authors.forename: Eisaku
authors.initials: E
authors.lastname: Miyauchi
authors.forename: Masaru
authors.initials: M
authors.lastname: Ushijima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Matsuura
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hirose
authors.forename: Naohiko
authors.initials: N
authors.lastname: Inase
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D012008:Recurrence; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000473:pathology
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding
keywords: HOTAIR; invasiveness; lincRNA; proliferation; small-cell lung cancer