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Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis
Long non-coding RNA SLC25A25 antisense RNA 1 (SLC25A25-AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25-AS1 is implicated in the aggressiveness of non-small cell lung cancer (NSCLC) and the possible underlying mechanism. SLC25A25-AS1 expression in...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138898/ https://www.ncbi.nlm.nih.gov/pubmed/34055094 http://dx.doi.org/10.3892/ol.2021.12790 |
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author | Chen, Jinqin Gao, Chengpeng Zhu, Wei |
author_facet | Chen, Jinqin Gao, Chengpeng Zhu, Wei |
author_sort | Chen, Jinqin |
collection | PubMed |
description | Long non-coding RNA SLC25A25 antisense RNA 1 (SLC25A25-AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25-AS1 is implicated in the aggressiveness of non-small cell lung cancer (NSCLC) and the possible underlying mechanism. SLC25A25-AS1 expression in NSCLC was determined by reverse transcription-quantitative PCR. The proliferation, apoptosis, migration and invasion of NSCLC cells were tested in vitro through cell counting kit-8 assay, flow cytometry analysis, Transwell migration and invasion assays, followed by in vivo validation using animal experiments. Additionally, the competitive endogenous RNA theory for SLC25A25-AS1, microRNA-195-5p (miR-195-5p) and integrin α2 (ITGA2) was identified using subcellular fractionation, bioinformatics analysis, reverse transcription-quantitative PCR, western blotting, a luciferase assay and RNA immunoprecipitation. As compared with normal lung tissues, increased expression of SLC25A25-AS1 was demonstrated in NSCLC tissues using The Cancer Genome Atlas database.. In addition, SLC25A25-AS1 was overexpressed in both NSCLC tissues and cell lines. High SLC25A25-AS1 expression was markedly associated with shorter overall survival time of patients with NSCLC. SLC25A25-AS1 silencing impeded NSCLC cell proliferation and triggered apoptosis, while restricting cell migration and invasion. Tumour growth in vivo was also impaired by SLC25A25-AS1 silencing. Mechanistically, SLC25A25-AS1 was demonstrated to be an miR-195-5p sponge in NSCLC cells. miR-195-5p mimics decreased ITGA2 expression in NSCLC cells by directly targeting ITGA2, and SLC25A25-AS1 interference decreased ITGA2 expression by sequestering miR-195-5p. Furthermore, the antitumour effects of SLC25A25-AS1 silencing on malignant behaviours were counteracted when ITGA2 was restored or when miR-195-5p was silenced. In summary, by controlling the miR-195-5p/ITGA2 axis, SLC25A25-AS1 served tumour-promoting roles in NSCLC cells. Therefore, the SLC25A25-AS1/miR-195-5p/ITGA2 signalling pathway might be an attractive target for future therapeutic options in NSCLC. |
format | Online Article Text |
id | pubmed-8138898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-81388982021-05-27 Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis Chen, Jinqin Gao, Chengpeng Zhu, Wei Oncol Lett Articles Long non-coding RNA SLC25A25 antisense RNA 1 (SLC25A25-AS1) exerts antitumour activity in colorectal cancer. The present study investigated whether SLC25A25-AS1 is implicated in the aggressiveness of non-small cell lung cancer (NSCLC) and the possible underlying mechanism. SLC25A25-AS1 expression in NSCLC was determined by reverse transcription-quantitative PCR. The proliferation, apoptosis, migration and invasion of NSCLC cells were tested in vitro through cell counting kit-8 assay, flow cytometry analysis, Transwell migration and invasion assays, followed by in vivo validation using animal experiments. Additionally, the competitive endogenous RNA theory for SLC25A25-AS1, microRNA-195-5p (miR-195-5p) and integrin α2 (ITGA2) was identified using subcellular fractionation, bioinformatics analysis, reverse transcription-quantitative PCR, western blotting, a luciferase assay and RNA immunoprecipitation. As compared with normal lung tissues, increased expression of SLC25A25-AS1 was demonstrated in NSCLC tissues using The Cancer Genome Atlas database.. In addition, SLC25A25-AS1 was overexpressed in both NSCLC tissues and cell lines. High SLC25A25-AS1 expression was markedly associated with shorter overall survival time of patients with NSCLC. SLC25A25-AS1 silencing impeded NSCLC cell proliferation and triggered apoptosis, while restricting cell migration and invasion. Tumour growth in vivo was also impaired by SLC25A25-AS1 silencing. Mechanistically, SLC25A25-AS1 was demonstrated to be an miR-195-5p sponge in NSCLC cells. miR-195-5p mimics decreased ITGA2 expression in NSCLC cells by directly targeting ITGA2, and SLC25A25-AS1 interference decreased ITGA2 expression by sequestering miR-195-5p. Furthermore, the antitumour effects of SLC25A25-AS1 silencing on malignant behaviours were counteracted when ITGA2 was restored or when miR-195-5p was silenced. In summary, by controlling the miR-195-5p/ITGA2 axis, SLC25A25-AS1 served tumour-promoting roles in NSCLC cells. Therefore, the SLC25A25-AS1/miR-195-5p/ITGA2 signalling pathway might be an attractive target for future therapeutic options in NSCLC. D.A. Spandidos 2021-07 2021-05-16 /pmc/articles/PMC8138898/ /pubmed/34055094 http://dx.doi.org/10.3892/ol.2021.12790 Text en Copyright: © Chen et al. https://creativecommons.org/licenses/by-nc-nd/4.0/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 Chen, Jinqin Gao, Chengpeng Zhu, Wei Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title | Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title_full | Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title_fullStr | Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title_full_unstemmed | Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title_short | Long non-coding RNA SLC25A25-AS1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microRNA-195-5p/ITGA2 axis |
title_sort | long non-coding rna slc25a25-as1 exhibits oncogenic roles in non-small cell lung cancer by regulating the microrna-195-5p/itga2 axis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138898/ https://www.ncbi.nlm.nih.gov/pubmed/34055094 http://dx.doi.org/10.3892/ol.2021.12790 |
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