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The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway
The action mechanism of long non-coding ribonucleic acid-homeobox transcript antisense ribonucleic acid (lncRNA-HOTAIR) in the regulation of the Wnt signaling pathway on the drug resistance of non-small cell lung cancer was investigated. Forty eight patients with non-small cell lung cancer, who were...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958754/ https://www.ncbi.nlm.nih.gov/pubmed/29805510 http://dx.doi.org/10.3892/etm.2018.6052 |
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author | Guo, Feng Cao, Zhili Guo, Huiqin Li, Shanqing |
author_facet | Guo, Feng Cao, Zhili Guo, Huiqin Li, Shanqing |
author_sort | Guo, Feng |
collection | PubMed |
description | The action mechanism of long non-coding ribonucleic acid-homeobox transcript antisense ribonucleic acid (lncRNA-HOTAIR) in the regulation of the Wnt signaling pathway on the drug resistance of non-small cell lung cancer was investigated. Forty eight patients with non-small cell lung cancer, who were treated with cisplatin (DDP) as neoadjuvant chemotherapy, were selected from the specimen bank of the Department of Pathology of Peking Union Medical College Hospital. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger RNA (mRNA) level of lncRNA-HOTAIR in cancer and cancer-adjacent tissues. The correlation curve of the expression of lncRNA-HOTAIR with the overall survival (OS) was plotted using the Kaplan-Meier method. NCI-H1299 DDP-resistant cell lines were constructed, and the half maximal inhibitory concentration (IC(50)) value was measured. The expression of lnc-HOTAIR in NCI-H1299/DDP cells was detected by the target interference of small interfering RNA (siRNA). The effect of si-HOTAIR on cell resistance was detected by Cell Counting Kit-8 (CCK-8). Western blot analysis was used to detect the effects of si-HOTAIR on multidrug resistance proteins, multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 1 (MDR1), and Wnt signaling pathways, Wnt3a, adenomatous polyposis coli (APC) and β-catenin. The mRNA level of lncRNA-HOTAIR in cancer tissues was significantly higher than that in cancer-adjacent tissues (P<0.05), and the high expression of lncRNA-HOTAIR indicated that the OS of patients was shortened (P<0.05). The IC(50) of NCI-H1299/DDP cells inhibiting DDP was 127.82 µM, which was significantly higher than that of parental NCI-H1299 cells (IC(50)=8.40 µM) (P<0.05). si-HOTAIR interference significantly decreased the sensitivity of cells to DDP, the IC(50) of cells was decreased from 131.85 to 44.34 µM (P<0.05), the expression levels of MRP1 and MDR1 were significantly decreased, and the activation of Wnt signaling pathway was significantly inhibited (P<0.05). Thus, lncRNA-HOTAIR plays an important role in the occurrence and development of non-small cell lung cancer, and it may be an important factor in the clinical prognosis of patients with non-small cell lung cancer. |
format | Online Article Text |
id | pubmed-5958754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-59587542018-05-27 The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway Guo, Feng Cao, Zhili Guo, Huiqin Li, Shanqing Exp Ther Med Articles The action mechanism of long non-coding ribonucleic acid-homeobox transcript antisense ribonucleic acid (lncRNA-HOTAIR) in the regulation of the Wnt signaling pathway on the drug resistance of non-small cell lung cancer was investigated. Forty eight patients with non-small cell lung cancer, who were treated with cisplatin (DDP) as neoadjuvant chemotherapy, were selected from the specimen bank of the Department of Pathology of Peking Union Medical College Hospital. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the messenger RNA (mRNA) level of lncRNA-HOTAIR in cancer and cancer-adjacent tissues. The correlation curve of the expression of lncRNA-HOTAIR with the overall survival (OS) was plotted using the Kaplan-Meier method. NCI-H1299 DDP-resistant cell lines were constructed, and the half maximal inhibitory concentration (IC(50)) value was measured. The expression of lnc-HOTAIR in NCI-H1299/DDP cells was detected by the target interference of small interfering RNA (siRNA). The effect of si-HOTAIR on cell resistance was detected by Cell Counting Kit-8 (CCK-8). Western blot analysis was used to detect the effects of si-HOTAIR on multidrug resistance proteins, multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 1 (MDR1), and Wnt signaling pathways, Wnt3a, adenomatous polyposis coli (APC) and β-catenin. The mRNA level of lncRNA-HOTAIR in cancer tissues was significantly higher than that in cancer-adjacent tissues (P<0.05), and the high expression of lncRNA-HOTAIR indicated that the OS of patients was shortened (P<0.05). The IC(50) of NCI-H1299/DDP cells inhibiting DDP was 127.82 µM, which was significantly higher than that of parental NCI-H1299 cells (IC(50)=8.40 µM) (P<0.05). si-HOTAIR interference significantly decreased the sensitivity of cells to DDP, the IC(50) of cells was decreased from 131.85 to 44.34 µM (P<0.05), the expression levels of MRP1 and MDR1 were significantly decreased, and the activation of Wnt signaling pathway was significantly inhibited (P<0.05). Thus, lncRNA-HOTAIR plays an important role in the occurrence and development of non-small cell lung cancer, and it may be an important factor in the clinical prognosis of patients with non-small cell lung cancer. D.A. Spandidos 2018-06 2018-04-11 /pmc/articles/PMC5958754/ /pubmed/29805510 http://dx.doi.org/10.3892/etm.2018.6052 Text en Copyright: © Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Guo, Feng Cao, Zhili Guo, Huiqin Li, Shanqing The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title | The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title_full | The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title_fullStr | The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title_full_unstemmed | The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title_short | The action mechanism of lncRNA-HOTAIR on the drug resistance of non-small cell lung cancer by regulating Wnt signaling pathway |
title_sort | action mechanism of lncrna-hotair on the drug resistance of non-small cell lung cancer by regulating wnt signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958754/ https://www.ncbi.nlm.nih.gov/pubmed/29805510 http://dx.doi.org/10.3892/etm.2018.6052 |
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