Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer

Hiroshi Ono, Noriko Motoi, Hiroko Nagano, Eisaku Miyauchi, Masaru Ushijima, Masaaki Matsuura, Sakae Okumura, Makoto Nishio, Tetsuro Hirose, Naohiko Inase, Yuichi Ishikawa

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)632-642
Number of pages11
JournalCancer medicine
Volume3
Issue number3
DOIs
Publication statusPublished - 2014 Jun 1
Externally publishedYes

Keywords

  • HOTAIR
  • invasiveness
  • lincRNA
  • proliferation
  • small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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