Long non-coding RNA HOTAIR in carcinogenesis and metastasis.

Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as a potentially new and crucial layer of gene regulation. LncRNAs are prevalently transcribed in the genome, but their roles in gene regulation and disease development are largely unknown. HOX antisense intergenic RNA (HOTAIR), a lncRNA located in the HOXC locus, has been shown to repress HOXD gene expression and promote breast cancer metastasis. Mechanistically, HOTAIR interacts with and recruits polycomb repressive complex 2 (PRC2) and regulates chromosome occupancy by EZH2 (a subunit of PRC2), which leads to histone H3 lysine 27 trimethylation of the HOXD locus. Moreover, HOTAIR is pervasively overexpressed in most human cancers compared with noncancerous adjacent tissues. This review summarizes the studies on the HOTAIR lncRNA over the past 6 years.

[1]  Howard Y. Chang,et al.  Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes , 2010, Science.

[2]  Ikuro Sato,et al.  Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. , 2013, Biochemical and biophysical research communications.

[3]  J. Rinn,et al.  Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression , 2009, Proceedings of the National Academy of Sciences.

[4]  M. Surani,et al.  Loss of Xist imprinting in diploid parthenogenetic preimplantation embryos. , 2001, Developmental biology.

[5]  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.

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

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

[8]  Shanling Liu,et al.  [Expression of long non-coding RNA HOTAIR mRNA in ovarian cancer]. , 2013, Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition.

[9]  P. Stadler,et al.  RNA Maps Reveal New RNA Classes and a Possible Function for Pervasive Transcription , 2007, Science.

[10]  Writer meets eraser in HOTAIR. , 2011, Acta biochimica et biophysica Sinica.

[11]  V. Bajic,et al.  On the classification of long non-coding RNAs , 2013, RNA biology.

[12]  Lu Gan,et al.  Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2 , 2010, Nature Cell Biology.

[13]  Bronwen L. Aken,et al.  GENCODE: The reference human genome annotation for The ENCODE Project , 2012, Genome research.

[14]  H. Yao,et al.  Long Noncoding RNA HOTAIR Is a Prognostic Marker for Esophageal Squamous Cell Carcinoma Progression and Survival , 2013, PloS one.

[15]  Erik K Flemington,et al.  Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen , 2013, Journal of Hematology & Oncology.

[16]  Jindan Yu,et al.  BRCA1 is a negative modulator of the PRC2 complex , 2013, The EMBO journal.

[17]  Q. Li,et al.  Large Intervening Non-Coding RNA HOTAIR is Associated with Hepatocellular Carcinoma Progression , 2011, The Journal of international medical research.

[18]  Patrick Schorderet,et al.  Structural and Functional Differences in the Long Non-Coding RNA Hotair in Mouse and Human , 2011, PLoS genetics.

[19]  R. Kingston,et al.  HOTAIR Lifts Noncoding RNAs to New Levels , 2007, Cell.

[20]  G. Wakabayashi,et al.  Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. , 2013, Oncology reports.

[21]  C. Gong,et al.  Long non‐coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival , 2013, Cancer science.

[22]  Ming Liu,et al.  Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. , 2013, The American journal of pathology.

[23]  Howard Y. Chang,et al.  Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. , 2011, Molecular cell.

[24]  A. Bhan,et al.  Antisense transcript long noncoding RNA (lncRNA) HOTAIR is transcriptionally induced by estradiol. , 2013, Journal of molecular biology.

[25]  M. Toyota,et al.  Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. , 2012, Cancer research.

[26]  R. Aharonov,et al.  Identification of hundreds of conserved and nonconserved human microRNAs , 2005, Nature Genetics.

[27]  D. Reinberg,et al.  Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. , 2010, Genes & development.

[28]  Gianluca Gregori,et al.  Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer , 2012, Breast Cancer Research and Treatment.

[29]  K. Leslie,et al.  Correlation of MTDH/AEG-1 and HOTAIR Expression with Metastasis and Response to Treatment in Sarcoma Patients. , 2011, Journal of cancer science & therapy.

[30]  Shiping Liu,et al.  The sequence, structure and evolutionary features of HOTAIR in mammals , 2011, BMC Evolutionary Biology.

[31]  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.

[32]  Haojie Huang,et al.  Phosphorylation of EZH2 by CDK1 and CDK2 , 2011, Cell cycle.

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