PMID- 23141928 OWN - NLM STAT- MEDLINE DCOM- 20130606 LR - 20220408 IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 182 IP - 1 DP - 2013 Jan TI - Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. PG - 64-70 LID - S0002-9440(12)00716-X [pii] LID - 10.1016/j.ajpath.2012.08.042 [doi] AB - 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. CI - Copyright (c) 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Li, Dandan AU - Li D AD - Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China. FAU - Feng, Jiapeng AU - Feng J FAU - Wu, Tianyi AU - Wu T FAU - Wang, Yandong AU - Wang Y FAU - Sun, Yanan AU - Sun Y FAU - Ren, Jingyuan AU - Ren J FAU - Liu, Ming AU - Liu M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121107 PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Biomarkers, Tumor) RN - 0 (DNA, Neoplasm) RN - 0 (HOTAIR long untranslated RNA, human) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Neoplasm) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Animals MH - Apoptosis/genetics MH - Biomarkers, Tumor/biosynthesis/genetics MH - Carcinoma, Squamous Cell/*genetics/metabolism/pathology MH - DNA Methylation/genetics MH - DNA, Neoplasm/genetics MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - Gene Knockdown Techniques MH - Genes, Neoplasm MH - Humans MH - Laryngeal Neoplasms/*genetics/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Middle Aged MH - Neoplasm Invasiveness MH - Neoplasm Transplantation MH - PTEN Phosphohydrolase/*genetics/metabolism MH - Prognosis MH - RNA, Long Noncoding/*biosynthesis/genetics MH - RNA, Neoplasm/genetics MH - Transplantation, Heterologous MH - Tumor Cells, Cultured EDAT- 2012/11/13 06:00 MHDA- 2013/06/07 06:00 CRDT- 2012/11/13 06:00 PHST- 2012/01/14 00:00 [received] PHST- 2012/07/03 00:00 [revised] PHST- 2012/08/23 00:00 [accepted] PHST- 2012/11/13 06:00 [entrez] PHST- 2012/11/13 06:00 [pubmed] PHST- 2013/06/07 06:00 [medline] AID - S0002-9440(12)00716-X [pii] AID - 10.1016/j.ajpath.2012.08.042 [doi] PST - ppublish SO - Am J Pathol. 2013 Jan;182(1):64-70. doi: 10.1016/j.ajpath.2012.08.042. Epub 2012 Nov 7.