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LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia
OBJECTIVE: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, accounting for approximately 70% of acute leukemias. Long noncoding RNA-DUXAP8 (lncRNA-DUXAP8) has been found to be abnormally expressed in a variety of tumors. However, its function and mechanism in AML have not be...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Galenos Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656122/ https://www.ncbi.nlm.nih.gov/pubmed/34431643 http://dx.doi.org/10.4274/tjh.galenos.2021.2020.0769 |
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author | Zhai, Hong Zhao, Junting Pu, Juan Zhao, Pan Wei, Jin |
author_facet | Zhai, Hong Zhao, Junting Pu, Juan Zhao, Pan Wei, Jin |
author_sort | Zhai, Hong |
collection | PubMed |
description | OBJECTIVE: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, accounting for approximately 70% of acute leukemias. Long noncoding RNA-DUXAP8 (lncRNA-DUXAP8) has been found to be abnormally expressed in a variety of tumors. However, its function and mechanism in AML have not been studied. We investigate the effect of lncRNA-DUXAP8 on AML and its mechanism so as to provide a new theoretical basis for the diagnosis and treatment of AML. MATERIALS AND METHODS: The expression of lncRNA-DUXAP8 in AML bone marrow tissues and the THP-1, HL-60, TF-1, AML193, and U937 cell lines was detected by qRT-PCR. It was then altered by transfecting plasmids overexpressing si-DUXAP8 and lncRNA-DUXAP8, respectively. CCK8 and cell colony assay were performed to evaluate the proliferation ability of AML cells. In addition, flow cytometry was used to observe the apoptosis process. Glucose and lactate kits were utilized to detect glucose consumption and lactate levels. Finally, western blotting was performed to detect the expression of proteins related to the Wnt/β-catenin signaling pathway in cells. RESULTS: LncRNA-DUXAP8 was downregulated in both AML bone marrow tissues and cell lines. Upon interfering with lncRNA-DUXAP8 in AML cell line THP-1, AML cell proliferation and glycolysis were promoted while cell apoptosis was inhibited. The opposite results were obtained after overexpressing lncRNA-DUXAP8. Meanwhile, western blotting confirmed that interference with lncRNA-DUXAP8 stimulated the expression of proteins Wnt5a, β-catenin, c-Myc, and cyclin-D1 in the Wnt/β-catenin pathway. Moreover, overexpression of lncRNA-DUXAP8 inhibited the expression of Wnt/β-catenin pathway proteins. Finally, LiCl, an activator of the Wnt/β-catenin pathway, reversed the regulation of AML cells by lncRNA-DUXAP8 upregulation compared with the DUXAP group. CONCLUSION: This study showed that lncRNA-DUXAP8 regulated the Wnt/β-catenin signaling pathway to inhibit glycolysis and induce apoptosis in AML. This experiment has provided new angles and an experimental basis for treating patients with AML. |
format | Online Article Text |
id | pubmed-8656122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Galenos Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-86561222021-12-16 LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia Zhai, Hong Zhao, Junting Pu, Juan Zhao, Pan Wei, Jin Turk J Haematol Research Article OBJECTIVE: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, accounting for approximately 70% of acute leukemias. Long noncoding RNA-DUXAP8 (lncRNA-DUXAP8) has been found to be abnormally expressed in a variety of tumors. However, its function and mechanism in AML have not been studied. We investigate the effect of lncRNA-DUXAP8 on AML and its mechanism so as to provide a new theoretical basis for the diagnosis and treatment of AML. MATERIALS AND METHODS: The expression of lncRNA-DUXAP8 in AML bone marrow tissues and the THP-1, HL-60, TF-1, AML193, and U937 cell lines was detected by qRT-PCR. It was then altered by transfecting plasmids overexpressing si-DUXAP8 and lncRNA-DUXAP8, respectively. CCK8 and cell colony assay were performed to evaluate the proliferation ability of AML cells. In addition, flow cytometry was used to observe the apoptosis process. Glucose and lactate kits were utilized to detect glucose consumption and lactate levels. Finally, western blotting was performed to detect the expression of proteins related to the Wnt/β-catenin signaling pathway in cells. RESULTS: LncRNA-DUXAP8 was downregulated in both AML bone marrow tissues and cell lines. Upon interfering with lncRNA-DUXAP8 in AML cell line THP-1, AML cell proliferation and glycolysis were promoted while cell apoptosis was inhibited. The opposite results were obtained after overexpressing lncRNA-DUXAP8. Meanwhile, western blotting confirmed that interference with lncRNA-DUXAP8 stimulated the expression of proteins Wnt5a, β-catenin, c-Myc, and cyclin-D1 in the Wnt/β-catenin pathway. Moreover, overexpression of lncRNA-DUXAP8 inhibited the expression of Wnt/β-catenin pathway proteins. Finally, LiCl, an activator of the Wnt/β-catenin pathway, reversed the regulation of AML cells by lncRNA-DUXAP8 upregulation compared with the DUXAP group. CONCLUSION: This study showed that lncRNA-DUXAP8 regulated the Wnt/β-catenin signaling pathway to inhibit glycolysis and induce apoptosis in AML. This experiment has provided new angles and an experimental basis for treating patients with AML. Galenos Publishing 2021-12 2021-12-07 /pmc/articles/PMC8656122/ /pubmed/34431643 http://dx.doi.org/10.4274/tjh.galenos.2021.2020.0769 Text en © Copyright 2021 by Turkish Society of Hematology / Turkish Journal of Hematology, Published by Galenos Publishing House. https://creativecommons.org/licenses/by/2.5/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhai, Hong Zhao, Junting Pu, Juan Zhao, Pan Wei, Jin LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title | LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title_full | LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title_fullStr | LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title_full_unstemmed | LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title_short | LncRNA-DUXAP8 Regulation of the Wnt/β-Catenin Signaling Pathway to Inhibit Glycolysis and Induced Apoptosis in Acute Myeloid Leukemia |
title_sort | lncrna-duxap8 regulation of the wnt/β-catenin signaling pathway to inhibit glycolysis and induced apoptosis in acute myeloid leukemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656122/ https://www.ncbi.nlm.nih.gov/pubmed/34431643 http://dx.doi.org/10.4274/tjh.galenos.2021.2020.0769 |
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