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Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression

Ototoxicity is the drug-induced damage of the inner ear, causing bilateral irreversible sensorineural hearing loss. Cisplatin is a widely used chemotherapeutic agent which causes ototoxicity as its side effect. Pretreatment with metformin prior to the application of cisplatin significantly decreased...

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Autores principales: Lee, Sehee, Choi, Sun, Park, Seok Hyun, Im, Gi Jung, Chang, Jiwon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857533/
https://www.ncbi.nlm.nih.gov/pubmed/36661507
http://dx.doi.org/10.3390/cimb45010021
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author Lee, Sehee
Choi, Sun
Park, Seok Hyun
Im, Gi Jung
Chang, Jiwon
author_facet Lee, Sehee
Choi, Sun
Park, Seok Hyun
Im, Gi Jung
Chang, Jiwon
author_sort Lee, Sehee
collection PubMed
description Ototoxicity is the drug-induced damage of the inner ear, causing bilateral irreversible sensorineural hearing loss. Cisplatin is a widely used chemotherapeutic agent which causes ototoxicity as its side effect. Pretreatment with metformin prior to the application of cisplatin significantly decreased the late apoptosis and attenuated the cisplatin-induced increase in ROS. To understand the molecular mechanisms that are involved in the preventive effect of metformin, we evaluated the change of gene expression induced by cisplatin at several different time points (0 h, 6 h, 15 h, 24 h and 48 h) and the alteration of gene expression according to pretreatment with metformin in HEI-OC1 cells through microarray analysis. Cisplatin exposure induced a total of 89 DEGs (differentially expressed genes) after 6 h, with a total of 433 DEGs after 15 h, a total of 941 DEGs after 24 h, and a total of 2764 DEGs after 48 h. When cells were pretreated with metformin for 24 h, we identified a total of 105 DEGs after 6 h of cisplatin exposure, a total of 257 DEGs after 15 h, a total of 1450 DEGs after 24 h, and a total of 1463 DEGs after 48 h. The analysis was performed based on the gene expression, network analyses, and qRT-PCR, and we identified several genes (CSF2, FOS, JUN, TNFα, NFκB, Txnip, ASK1, TXN2, ATF3, TP53, IL6, and IGF1) as metformin-related preventive biomarkers in cisplatin ototoxicity.
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spelling pubmed-98575332023-01-21 Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression Lee, Sehee Choi, Sun Park, Seok Hyun Im, Gi Jung Chang, Jiwon Curr Issues Mol Biol Article Ototoxicity is the drug-induced damage of the inner ear, causing bilateral irreversible sensorineural hearing loss. Cisplatin is a widely used chemotherapeutic agent which causes ototoxicity as its side effect. Pretreatment with metformin prior to the application of cisplatin significantly decreased the late apoptosis and attenuated the cisplatin-induced increase in ROS. To understand the molecular mechanisms that are involved in the preventive effect of metformin, we evaluated the change of gene expression induced by cisplatin at several different time points (0 h, 6 h, 15 h, 24 h and 48 h) and the alteration of gene expression according to pretreatment with metformin in HEI-OC1 cells through microarray analysis. Cisplatin exposure induced a total of 89 DEGs (differentially expressed genes) after 6 h, with a total of 433 DEGs after 15 h, a total of 941 DEGs after 24 h, and a total of 2764 DEGs after 48 h. When cells were pretreated with metformin for 24 h, we identified a total of 105 DEGs after 6 h of cisplatin exposure, a total of 257 DEGs after 15 h, a total of 1450 DEGs after 24 h, and a total of 1463 DEGs after 48 h. The analysis was performed based on the gene expression, network analyses, and qRT-PCR, and we identified several genes (CSF2, FOS, JUN, TNFα, NFκB, Txnip, ASK1, TXN2, ATF3, TP53, IL6, and IGF1) as metformin-related preventive biomarkers in cisplatin ototoxicity. MDPI 2022-12-31 /pmc/articles/PMC9857533/ /pubmed/36661507 http://dx.doi.org/10.3390/cimb45010021 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Sehee
Choi, Sun
Park, Seok Hyun
Im, Gi Jung
Chang, Jiwon
Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title_full Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title_fullStr Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title_full_unstemmed Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title_short Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene Expression
title_sort transcriptomic analysis of the effect of metformin against cisplatin-induced ototoxicity: a potential mechanism of metformin-mediated inhibition of thioredoxin-interacting protein (txnip) gene expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857533/
https://www.ncbi.nlm.nih.gov/pubmed/36661507
http://dx.doi.org/10.3390/cimb45010021
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