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Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy of the digestive system with increasing incidence and mortality rates. The biological roles of microRNA (miR)-378a-3p in tumor cells remain contested, and the mechanisms underlying the functions, energy metabolism, and cell surviv...

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Autores principales: Qu, Yuan, Xue, Shan, Zheng, Yujian, Du, Yajing, Zhang, Guoping, Huang, Liting, Li, Hui, Li, Huiwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472027/
https://www.ncbi.nlm.nih.gov/pubmed/37664650
http://dx.doi.org/10.3892/ol.2023.14007
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author Qu, Yuan
Xue, Shan
Zheng, Yujian
Du, Yajing
Zhang, Guoping
Huang, Liting
Li, Hui
Li, Huiwu
author_facet Qu, Yuan
Xue, Shan
Zheng, Yujian
Du, Yajing
Zhang, Guoping
Huang, Liting
Li, Hui
Li, Huiwu
author_sort Qu, Yuan
collection PubMed
description Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy of the digestive system with increasing incidence and mortality rates. The biological roles of microRNA (miR)-378a-3p in tumor cells remain contested, and the mechanisms underlying the functions, energy metabolism, and cell survival mechanisms in ESCC cells are yet to be fully elucidated. In the present study, miR-378a-3p overexpression and negative control plasmids were transfected into ECA-109 cells using electroporation. Western blotting was used to detect the relative expression of proteins, and flow cytometry was used to detect cell apoptosis. Subsequently, ELISA assays were performed to determine enzyme activity, and an ATP detection kit was used to measure ATP content. Dual-luciferase reporter assays were performed to identify the target genes of miR-378a-3p. The results of the present study demonstrated that miR-378a-3p inhibited the gene expression and enzyme activities of glucose transporter protein 1 (GLUT-1), Aldolase A (ALDOA), and pyruvate kinase M2 (PKM2), all of which are involved in the glycolytic pathway of cells. Energy metabolism was suppressed by miR-378a-3p by reducing ATP content, and this downregulated the expression of Bcl-2 and Survivin. Moreover, increased miR-378a-3p expression promoted cell apoptosis in the early stages by increasing the expression levels and the activity of Bad and Caspase-3, while inhibiting the expression levels of Bcl-2 and Survivin. The results of the present study also demonstrated that GLUT-1/ALDOA/PKM2 were target genes of miR-378a-3p. Notably, miR-378a-3p blocked energy production and promoted the apoptosis of tumor cells via the downregulation of glycolytic enzyme expression and by reducing the mitochondrial membrane potential in ESCC. Bad, Caspase-3, Survivin, and Bcl-2 may be associated with blocking energy production and promoting apoptosis via miR-378a-3p in ESCC cells.
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spelling pubmed-104720272023-09-02 Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma Qu, Yuan Xue, Shan Zheng, Yujian Du, Yajing Zhang, Guoping Huang, Liting Li, Hui Li, Huiwu Oncol Lett Articles Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy of the digestive system with increasing incidence and mortality rates. The biological roles of microRNA (miR)-378a-3p in tumor cells remain contested, and the mechanisms underlying the functions, energy metabolism, and cell survival mechanisms in ESCC cells are yet to be fully elucidated. In the present study, miR-378a-3p overexpression and negative control plasmids were transfected into ECA-109 cells using electroporation. Western blotting was used to detect the relative expression of proteins, and flow cytometry was used to detect cell apoptosis. Subsequently, ELISA assays were performed to determine enzyme activity, and an ATP detection kit was used to measure ATP content. Dual-luciferase reporter assays were performed to identify the target genes of miR-378a-3p. The results of the present study demonstrated that miR-378a-3p inhibited the gene expression and enzyme activities of glucose transporter protein 1 (GLUT-1), Aldolase A (ALDOA), and pyruvate kinase M2 (PKM2), all of which are involved in the glycolytic pathway of cells. Energy metabolism was suppressed by miR-378a-3p by reducing ATP content, and this downregulated the expression of Bcl-2 and Survivin. Moreover, increased miR-378a-3p expression promoted cell apoptosis in the early stages by increasing the expression levels and the activity of Bad and Caspase-3, while inhibiting the expression levels of Bcl-2 and Survivin. The results of the present study also demonstrated that GLUT-1/ALDOA/PKM2 were target genes of miR-378a-3p. Notably, miR-378a-3p blocked energy production and promoted the apoptosis of tumor cells via the downregulation of glycolytic enzyme expression and by reducing the mitochondrial membrane potential in ESCC. Bad, Caspase-3, Survivin, and Bcl-2 may be associated with blocking energy production and promoting apoptosis via miR-378a-3p in ESCC cells. D.A. Spandidos 2023-08-10 /pmc/articles/PMC10472027/ /pubmed/37664650 http://dx.doi.org/10.3892/ol.2023.14007 Text en Copyright: © Qu 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
Qu, Yuan
Xue, Shan
Zheng, Yujian
Du, Yajing
Zhang, Guoping
Huang, Liting
Li, Hui
Li, Huiwu
Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title_full Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title_fullStr Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title_full_unstemmed Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title_short Upregulated miR‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a GLUT‑1/ALDOA/PKM2 axis in esophageal carcinoma
title_sort upregulated mir‑378a‑3p expression suppresses energy metabolism and promotes apoptosis by targeting a glut‑1/aldoa/pkm2 axis in esophageal carcinoma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472027/
https://www.ncbi.nlm.nih.gov/pubmed/37664650
http://dx.doi.org/10.3892/ol.2023.14007
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