Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer

Abstract

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.

HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis

“…16,17 Accumulating studies have indicated that HOTAIR is upregulated in cancers including HCC. [18][19][20] It has been reported that HOTAIR regulates gene expression via epigenetic modifications. 21 For example, Rinn et al demonstrated that HOTAIR interacts with polycomb-repressive complex 2 (PRC2) to increase the trimethylation of histone H3 lysine-27 (H3K27), resulting in the reduction of HOXD gene expression.…”

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis

“…However, in our study, significant correlations were not observed between HOTAIR and the ER status. Lu et al (35) detected HOTAIR expression using qRT-PCR in 336 breast cancer patients and found no significant associations with the ER status. Indeed, ER-negative tumors appear to have higher HOTAIR levels, although the difference is not statistically significant (p= 0.11) (35).…”

“…Lu et al (35) detected HOTAIR expression using qRT-PCR in 336 breast cancer patients and found no significant associations with the ER status. Indeed, ER-negative tumors appear to have higher HOTAIR levels, although the difference is not statistically significant (p= 0.11) (35). In our study, the level of HOTAIR expression was significantly higher in ER-negative AN3CA cells than in ER-positive endometrial cells (data not shown).…”

Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer

“…Gupta et al (5) first discovered that HOTAIR (Hox transcript antisense intergenic RNA) is one of the cancer metastasis-associated lncRNAs, and is a powerful biomarker of breast cancer metastasis and poor prognosis. Many other groups successively reported that HOTAIR overexpression is linked to the malignant features of many other cancer types (6)(7)(8)(9)(10)(11)(12)(13). Moreover, Rinn et al (14) and Tsai et al (15) suggested that HOTAIR lncRNA serves as a scaffold for at least two histone modification complexes in Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer order to induce transcriptional silencing of hundreds of genes including tumor-suppressor genes.…”