Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer

BACKGROUND: Increasing evidence has uncovered the anticancer activity of lidocaine in many cancers. However, the role and the underlying molecular mechanism of lidocaine in colorectal cancer (CRC) remain poorly understood. MATERIALS AND METHODS: Cell viability and apoptosis were measured by cell cou...

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Autores principales: Du, Juan, Zhang, Liying, Ma, Hongzhong, Wang, Yang, Wang, Pengpeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323806/
https://www.ncbi.nlm.nih.gov/pubmed/32612388
http://dx.doi.org/10.2147/CMAR.S244973
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author Du, Juan
Zhang, Liying
Ma, Hongzhong
Wang, Yang
Wang, Pengpeng
author_facet Du, Juan
Zhang, Liying
Ma, Hongzhong
Wang, Yang
Wang, Pengpeng
author_sort Du, Juan
collection PubMed
description BACKGROUND: Increasing evidence has uncovered the anticancer activity of lidocaine in many cancers. However, the role and the underlying molecular mechanism of lidocaine in colorectal cancer (CRC) remain poorly understood. MATERIALS AND METHODS: Cell viability and apoptosis were measured by cell counting kit-8 assay and flow cytometry. Western blot was used to detect the protein of p53, CyclinD1, Pro-caspase-3, Cleaved-caspase-3, Pro-caspase-9, Cleaved-caspase-9, and hes-related family bHLH transcription factor with YRPW motif 1 (HEY1). Glycolytic metabolism was calculated by measuring the glucose consumption, lactate production and adenosine triphosphate (ATP) contents. The expression of circRNA homer scaffold protein 1 (circHOMER1), microRNA (miR)-138-5p and HEY1 mRNA was detected by quantitative real-time polymerase chain reaction. The interaction between miR-138-5p and circHOMER1 or HEY1 was analyzed using the dual-luciferase reporter assay. In vivo experiments were performed using the murine xenograft model. RESULTS: Lidocaine suppressed CRC cell viability and aerobic glycolysis but promoted cell apoptosis in vitro as well as hindered tumor growth in vivo. CircHOMER1 was elevated in CRC tissues and cells, while lidocaine decreased circHOMER1 expression in CRC cells. Additionally, circHOMER1 overexpression reversed the anti-tumor activity of lidocaine in CRC cells. miR-138-5p was confirmed to interact with circHOMER1 and HEY1 in CRC cells directly, and circHOMER1 regulated HEY1 expression through repressing miR-138-5p expression. Besides, rescue assay indicated the anti-tumor activity mediated by lidocaine could be regulated by circHOMER1/miR-138-5p/HEY1 axis. CONCLUSION: Lidocaine mediated CRC cell viability loss, apoptosis induction and aerobic glycolysis inhibition by regulating circHOMER1/miR-138-5p/HEY1 axis, providing a novel treatment option for lidocaine to prevent the progression of CRC.
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spelling pubmed-73238062020-06-30 Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer Du, Juan Zhang, Liying Ma, Hongzhong Wang, Yang Wang, Pengpeng Cancer Manag Res Original Research BACKGROUND: Increasing evidence has uncovered the anticancer activity of lidocaine in many cancers. However, the role and the underlying molecular mechanism of lidocaine in colorectal cancer (CRC) remain poorly understood. MATERIALS AND METHODS: Cell viability and apoptosis were measured by cell counting kit-8 assay and flow cytometry. Western blot was used to detect the protein of p53, CyclinD1, Pro-caspase-3, Cleaved-caspase-3, Pro-caspase-9, Cleaved-caspase-9, and hes-related family bHLH transcription factor with YRPW motif 1 (HEY1). Glycolytic metabolism was calculated by measuring the glucose consumption, lactate production and adenosine triphosphate (ATP) contents. The expression of circRNA homer scaffold protein 1 (circHOMER1), microRNA (miR)-138-5p and HEY1 mRNA was detected by quantitative real-time polymerase chain reaction. The interaction between miR-138-5p and circHOMER1 or HEY1 was analyzed using the dual-luciferase reporter assay. In vivo experiments were performed using the murine xenograft model. RESULTS: Lidocaine suppressed CRC cell viability and aerobic glycolysis but promoted cell apoptosis in vitro as well as hindered tumor growth in vivo. CircHOMER1 was elevated in CRC tissues and cells, while lidocaine decreased circHOMER1 expression in CRC cells. Additionally, circHOMER1 overexpression reversed the anti-tumor activity of lidocaine in CRC cells. miR-138-5p was confirmed to interact with circHOMER1 and HEY1 in CRC cells directly, and circHOMER1 regulated HEY1 expression through repressing miR-138-5p expression. Besides, rescue assay indicated the anti-tumor activity mediated by lidocaine could be regulated by circHOMER1/miR-138-5p/HEY1 axis. CONCLUSION: Lidocaine mediated CRC cell viability loss, apoptosis induction and aerobic glycolysis inhibition by regulating circHOMER1/miR-138-5p/HEY1 axis, providing a novel treatment option for lidocaine to prevent the progression of CRC. Dove 2020-06-25 /pmc/articles/PMC7323806/ /pubmed/32612388 http://dx.doi.org/10.2147/CMAR.S244973 Text en © 2020 Du et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Du, Juan
Zhang, Liying
Ma, Hongzhong
Wang, Yang
Wang, Pengpeng
Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title_full Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title_fullStr Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title_full_unstemmed Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title_short Lidocaine Suppresses Cell Proliferation and Aerobic Glycolysis by Regulating circHOMER1/miR-138-5p/HEY1 Axis in Colorectal Cancer
title_sort lidocaine suppresses cell proliferation and aerobic glycolysis by regulating circhomer1/mir-138-5p/hey1 axis in colorectal cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323806/
https://www.ncbi.nlm.nih.gov/pubmed/32612388
http://dx.doi.org/10.2147/CMAR.S244973
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