Overexpression of lncRNA HOXA11-AS promotes cell epithelial-mesenchymal transition by repressing miR-200b in non-small cell lung cancer
| Autor: | Suo Xu, Yu-Long Zheng, Chengping Hu, Jian-Hui Chen, Liyang Zhou, Yu-Feng Wan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Biology lcsh:RC254-282 miR-200b 03 medical and health sciences 0302 clinical medicine Gentamicin protection assay Transcription (biology) Genetics medicine Epithelial–mesenchymal transition EZH2 lcsh:QH573-671 Transcription factor Gene knockdown lcsh:Cytology DNMT1 lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens HOXA11-AS respiratory tract diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Primary Research Chromatin immunoprecipitation |
| Zdroj: | Cancer Cell International Cancer Cell International, Vol 17, Iss 1, Pp 1-11 (2017) |
| ISSN: | 1475-2867 |
| Popis: | Background Recent studies have verified that long noncoding RNAs (lncRNAs) involved in many biological functions and play crucial roles in human cancers progression, the study aimed to detect the association between long non-coding RNA HOXA11-AS and epithelial–mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC). Methods The lncRNA HOXA11-AS expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assays in 78 paired of tumor tissue and adjacent normal tissue samples in NSCLC patients. Kaplan–Meier survival curves and log-rank test was used to examine the association between lncRNA HOXA11-AS expression and the over survival time in NSCLC patients. Transwell invasion assay was performed to detect the cell invasion ability. QRT-PCR and western-blot analysis detected the mRNA and protein expression of EMT related transcription factors ZEB1/ZEB2, Snail1/2 and EMT marker E-cadherin and N-cadherin in NSCLC cells. RIP and Chromatin immunoprecipitation assays were performed to analyze the association between lncRNA HOXA11-AS and miR-200b expression in NSCLC cells. Results The lncRNA HOXA11-AS expression levels were significantly higher in NSCLC tissues compared with adjacent normal tissues and higher HOXA11-AS expression levels had a poor prognosis in NSCLC patients. Furthermore, knockdown of lncRNA HOXA11-AS in A549 and H1299 cells dramatically inhibited cell invasive abilities. Besides, the transcription levels and protein levels of EMT related transcription factors ZEB1/ZEB2, Snail1/2, and EMT maker N-cadherin were down-regulated after lncRNA HOXA11-AS was knocked down, but the mRNA and protein expression levels of EMT maker E-cadherin was increasing in A549 and H1299 cells. The mechanistic findings showed demonstrated that HOXA11-AS interacted with EZH2 and DNMT1 and recruited them to the miR-200b promoter regions to repress miR-200b expression in NSCLC cells, which promoted cell EMT in NSCLC. Conclusions Our results showed that up-regulation of lncRNA HOXA11-AS predicted a poor prognosis and lncRNA HOXA11-AS promoted cell epithelial–mesenchymal transition (EMT) by inhibiting miR-200b expression in NSCLC. |
| Databáze: | OpenAIRE |
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