HOX transcript antisense intergenic RNA represses E-cadherin expression by binding to EZH2 in gastric cancer
| Autor: | Xue-Feng Jia, Hai-Bo Zhao, Yongqian Shu, Wei-Dong Chen, Wen-Ming Chen, Qiu-Jie Zhang, Xue-Mei Jiang, Hong-Mei Wang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Kaplan-Meier Estimate 0302 clinical medicine Intergenic region Cell Movement Gene Knockdown Techniques RNA Small Interfering Promoter Regions Genetic Hox gene Regulation of gene expression Gastroenterology General Medicine Basic Study Middle Aged Cadherins Prognosis Immunohistochemistry HOX transcript antisense intergenic RNA Long non-coding RNA Up-Regulation Gene Expression Regulation Neoplastic Lymphatic Metastasis 030220 oncology & carcinogenesis embryonic structures Female RNA Long Noncoding Chromatin Immunoprecipitation animal structures macromolecular substances Biology Real-Time Polymerase Chain Reaction 03 medical and health sciences Antigens CD Stomach Neoplasms Cell Line Tumor Biomarkers Tumor Humans Migration and invasion Enhancer of Zeste Homolog 2 Protein Neoplasm Invasiveness RNA Messenger Neoplasm Staging Cadherin E-cadherin RNA Molecular biology 030104 developmental biology Gastric cancer Chromatin immunoprecipitation Long noncoding RNA Follow-Up Studies |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 1007-9327 |
| DOI: | 10.3748/wjg.v23.i33.6100 |
| Popis: | AIM To clarify the mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in gastric cancer (GC) migration and invasion. METHODS Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve (AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qPCR, western blot and immunohistochemistry were used to evaluate the mRNA and protein expression of E-cadherin. RNA-binding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin. RESULTS The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues (P < 0.001). Its over-expression was correlated with tumor-node-metastasis (TNM) stage (P = 0.024), tumor invasion (P = 0.018), lymph node metastasis (P = 0.023), and poor prognosis (P < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival (P = 0.033), together with TNM stage (P = 0.002) and lymph node metastasis (P = 0.002). The AUCROC was up to 0.709 (95%CI: 0.623-0.785, P < 0.001). Knockdown of HOTAIR by siRNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines, and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC. |
| Databáze: | OpenAIRE |
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