Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer
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Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12, interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene activities. Recent work suggests that it may have effects on breast cancer progression and survival. We evaluated HOTAIR expression and the methylation status of its downstream intergenic CpG island in primary breast cancers, and examined associations of these factors with clinical and pathologic features and patient survival. HOTAIR expression and DNA methylation were analyzed in tissue from 348 primary breast cancers with quantitative RT-PCR and methylation-specific PCR, respectively. HOTAIR expression and methylation varied widely in the tissues. A positive correlation was found between DNA methylation and HOTAIR expression. Methylation was associated with unfavorable disease characteristics, whereas no significant associations were found between HOTAIR expression and clinical or pathologic features. In multivariate, but not in univariate, Cox proportional hazard regression models, patients with high HOTAIR expression had lower risks of relapse and mortality than those with low HOTAIR expression. These findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies.
KeywordsLarge non-coding RNA DNA methylation Gene expression Breast cancer Prognosis
Conflict of interest
The authors declare that there are no conflicts of interest.
- 2.Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672PubMedCrossRefGoogle Scholar
- 12.Lu L, Katsaros D, Wiley A, Rigault de la Longrais IA, Risch HA, Puopolo M, Yu H (2006) The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 12:1208–1214PubMedCrossRefGoogle Scholar
- 13.Mu L, Katsaros D, Wiley A, Lu L, de la Longrais IA, Smith S, Khubchandani S, Sochirca O, Arisio R, Yu H (2009) Peptide concentrations and mRNA expression of IGF-I, IGF-II and IGFBP-3 in breast cancer and their associations with disease characteristics. Breast Cancer Res Treat 115:151–162PubMedCrossRefGoogle Scholar
- 18.Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S (2012) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. doi: 10.1038/onc.2012.193.