Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer.

HOTAIR is one of long non-coding RNAs and its expression correlates with the prognosis and metastasis in various cancers. We showed that HOTAIR expression has an important role in the development of non-small cell lung cancer (NSCLC). In this study, we examined the expression of HOTAIR in 77 NSCLCs, their corresponding normal lung tissues and 6 brain metastases by quantitative real-time RT-PCR. High expression of HOTAIR (tumor/normal ratio ⩾2) was detected in 17 patients (22.1%) and was frequently found in patients with advanced stage, lymph node metastasis or lymph-vascular invasion and short disease free interval. Furthermore, brain metastases show significantly higher HOTAIR expression compared to primary cancer tissues. HOTAIR-expressing A549 cells showed induced cell migration and anchorage-independent cell growth in vitro. These results indicate the expression of HOTAIR enhanced the aggressive behavior of NSCLC cells.

[1]  S. Miyano,et al.  Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. , 2011, Cancer research.

[2]  S. Shabalina,et al.  The mammalian transcriptome and the function of non-coding DNA sequences , 2004, Genome Biology.

[3]  Michael Thomas,et al.  MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer , 2003, Oncogene.

[4]  C. Croce,et al.  Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  A. Gemma,et al.  F1000 highlights , 2010 .

[6]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[7]  Howard Y. Chang,et al.  Long noncoding RNA HOTAIR reprograms chromatin state to promote cancer metastasis , 2010, Nature.

[8]  E. Hay.  An overview of epithelio-mesenchymal transformation. , 1995, Acta anatomica.

[9]  Jean Paul Thiery,et al.  Epithelial-mesenchymal transitions in development and pathologies. , 2003, Current opinion in cell biology.

[10]  Wan L. Lam,et al.  Mechanistic Roles of Noncoding RNAs in Lung Cancer Biology and Their Clinical Implications , 2012, Genetics research international.

[11]  Thomas D. Schmittgen,et al.  Analyzing real-time PCR data by the comparative CT method , 2008, Nature Protocols.

[12]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[13]  Guanghai Yang,et al.  MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). , 2010, Clinica chimica acta; international journal of clinical chemistry.

[14]  Y. Yatabe,et al.  A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. , 2005, Cancer research.

[15]  Gary Ruvkun,et al.  Glimpses of a Tiny RNA World , 2001, Science.

[16]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[17]  Thomas D. Schmittgen,et al.  Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. , 2007, Cancer cell.

[18]  A. G. Herreros,et al.  The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells , 2000, Nature Cell Biology.

[19]  Paul T. Groth,et al.  The ENCODE (ENCyclopedia Of DNA Elements) Project , 2004, Science.

[20]  I. Fabregat,et al.  Snail blocks the cell cycle and confers resistance to cell death. , 2004, Genes & development.

[21]  R. Stephens,et al.  Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. , 2006, Cancer cell.

[22]  Renato Martins,et al.  Erlotinib in previously treated non-small-cell lung cancer. , 2005, The New England journal of medicine.

[23]  E. Miyaoka,et al.  Japanese Lung Cancer Registry Study: First Prospective Enrollment of a Large Number of Surgical and Nonsurgical Cases in 2002 , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[24]  Haiyang Xie,et al.  Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation , 2011, Annals of Surgical Oncology.

[25]  Feng Jiang,et al.  Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers , 2011, BMC Cancer.

[26]  A. Schetter,et al.  MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers , 2009, Proceedings of the National Academy of Sciences.

[27]  S. Safe,et al.  HOTAIR IS A NEGATIVE PROGNOSTIC FACTOR AND EXHIBITS PRO-ONCOGENIC ACTIVITY IN PANCREATIC CANCER , 2012, Oncogene.

[28]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[29]  T. Kitamura,et al.  Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. , 2003, Experimental hematology.

[30]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[31]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[32]  H. Aburatani,et al.  Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer , 2007, Nature.

[33]  Yanqin Sun,et al.  miR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. , 2010, Biochemical and biophysical research communications.

[34]  Howard Y. Chang,et al.  Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs , 2007, Cell.