lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway

Long non-coding RNA (lncRNA) DGCR5 has been identified as a tumor suppressor in several types of cancer. However, its biological functions in pancreatic cancer (PaCa) have not yet been fully elucidated. The present study was designed to investigate the role of lncRNA DGCR5 in the regulation of PaCa...

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Autores principales: Li, Xianjie, Zhou, Shanxue, Fan, Tianyi, Feng, Xuefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307863/
https://www.ncbi.nlm.nih.gov/pubmed/32626951
http://dx.doi.org/10.3892/ijmm.2020.4632
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author Li, Xianjie
Zhou, Shanxue
Fan, Tianyi
Feng, Xuefeng
author_facet Li, Xianjie
Zhou, Shanxue
Fan, Tianyi
Feng, Xuefeng
author_sort Li, Xianjie
collection PubMed
description Long non-coding RNA (lncRNA) DGCR5 has been identified as a tumor suppressor in several types of cancer. However, its biological functions in pancreatic cancer (PaCa) have not yet been fully elucidated. The present study was designed to investigate the role of lncRNA DGCR5 in the regulation of PaCa cell apoptosis. For this purpose, lncRNA DGCR5, miR-27a-3p and Bcl-2/adenovirus E1B-19kDa-interacting protein 3 (BNIP3) expression levels were examined by reverse transcription-quantitative (RT-qPCR) and western blot analysis, respectively. RNA pull-down assay was used to verify DGCR5 as a target of miR-27a-3p and dual luciferase reporter assay was used to clarify whether miR-27a-3p targets the BNIP3 3′ UTR. In addition, PaCa cell apoptosis was assessed by flow cytometry. Recombinant plasmids and cell transfection were performed to modulate the endogenous expression of related genes. Thereafter, the role of DGCR5 in PaCa was analyzed using a nude mouse model of PaCa. lncRNA DGCR5 was found to be downregulated in PaCa tissues and cells. DGCR5 functioned as a decoy of miR-27a-3p, and BNIP3 was negatively regulated by miR-27a-3p. Following the transfection of DGCR5 plasmid into PaCa cells, the expression of miR-27a-3p was downregulated, and this downregulation was reversed following transfection with miR-27a-3p mimic. In addition, DGCR5 regulated the BNIP3 and p38 MAPK pathways via miR-27a-3p and promoted PaCa cell apoptosis via the miR-27a-3p/BNIP3 pathway. The results of in vivo experiments also indicated the positive effects of DGCR5 on a nude mouse model of PaCa. On the whole, the findings of the present study indicate that lncRNA DGCR5 upregulates the BNIP3 and p38 MAPK pathways via miR-27a-3p to promote PaCa cell apoptosis, thereby attenuating PaCa development.
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spelling pubmed-73078632020-06-23 lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway Li, Xianjie Zhou, Shanxue Fan, Tianyi Feng, Xuefeng Int J Mol Med Articles Long non-coding RNA (lncRNA) DGCR5 has been identified as a tumor suppressor in several types of cancer. However, its biological functions in pancreatic cancer (PaCa) have not yet been fully elucidated. The present study was designed to investigate the role of lncRNA DGCR5 in the regulation of PaCa cell apoptosis. For this purpose, lncRNA DGCR5, miR-27a-3p and Bcl-2/adenovirus E1B-19kDa-interacting protein 3 (BNIP3) expression levels were examined by reverse transcription-quantitative (RT-qPCR) and western blot analysis, respectively. RNA pull-down assay was used to verify DGCR5 as a target of miR-27a-3p and dual luciferase reporter assay was used to clarify whether miR-27a-3p targets the BNIP3 3′ UTR. In addition, PaCa cell apoptosis was assessed by flow cytometry. Recombinant plasmids and cell transfection were performed to modulate the endogenous expression of related genes. Thereafter, the role of DGCR5 in PaCa was analyzed using a nude mouse model of PaCa. lncRNA DGCR5 was found to be downregulated in PaCa tissues and cells. DGCR5 functioned as a decoy of miR-27a-3p, and BNIP3 was negatively regulated by miR-27a-3p. Following the transfection of DGCR5 plasmid into PaCa cells, the expression of miR-27a-3p was downregulated, and this downregulation was reversed following transfection with miR-27a-3p mimic. In addition, DGCR5 regulated the BNIP3 and p38 MAPK pathways via miR-27a-3p and promoted PaCa cell apoptosis via the miR-27a-3p/BNIP3 pathway. The results of in vivo experiments also indicated the positive effects of DGCR5 on a nude mouse model of PaCa. On the whole, the findings of the present study indicate that lncRNA DGCR5 upregulates the BNIP3 and p38 MAPK pathways via miR-27a-3p to promote PaCa cell apoptosis, thereby attenuating PaCa development. D.A. Spandidos 2020-08 2020-06-04 /pmc/articles/PMC7307863/ /pubmed/32626951 http://dx.doi.org/10.3892/ijmm.2020.4632 Text en Copyright: © Li 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
Li, Xianjie
Zhou, Shanxue
Fan, Tianyi
Feng, Xuefeng
lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title_full lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title_fullStr lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title_full_unstemmed lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title_short lncRNA DGCR 5/miR-27a-3p/BNIP3 promotes cell apoptosis in pancreatic cancer by regulating the p38 MAPK pathway
title_sort lncrna dgcr 5/mir-27a-3p/bnip3 promotes cell apoptosis in pancreatic cancer by regulating the p38 mapk pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307863/
https://www.ncbi.nlm.nih.gov/pubmed/32626951
http://dx.doi.org/10.3892/ijmm.2020.4632
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