Long Intergenic Noncoding RNA HOTAIR Is Overexpressed and Regulates PTEN Methylation in Laryngeal Squamous Cell Carcinoma

Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic noncoding RNA (lincRNA) that is significantly overexpressed in breast and hepatocellular cancers. It remains unclear, however, whether HOTAIR plays an oncogenic role in human Laryngeal squamous cell cancer (LSCC). We therefore investigated the expression and functional role of HOTAIR in LSCC. HOTAIR levels were significantly higher in LSCC than in corresponding adjacent non-neoplastic tissues, and patients with poor histological grade or advanced clinical stage had higher HOTAIR expression. Log-rank test showed a significant association between high Levels of HOTAIR and poor prognosis in LSCC patients. Multivariate Cox analysis suggested that HOTAIR is an independent prognostic factor of LSCC. siRNA-mediated knockdown of HOTAIR led to reduced invasion and increased apoptosis of Hep-2 cells in vitro and significantly reduced growth of LSCC xenograft tumors in mice. Moreover, PTEN methylation was significantly reduced in Hep-2 cells depleted of HOTAIR. Taken together, these results suggest that the oncogenic role of HOTAIR in LSCC is related to promotion of PTEN methylation. HOTAIR could serve as a marker for LSCC prognosis and a potential target for therapeutic intervention. (Am J Pathol 2013, 182: 64-70; http://dx.doi.org/10.1016/j.ajpath.2012.08.042)