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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MDPI AG
2022-12-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/45/1/21 |
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| author | Sehee Lee Sun Choi Seok Hyun Park Gi Jung Im Jiwon Chang |
| author_facet | Sehee Lee Sun Choi Seok Hyun Park Gi Jung Im Jiwon Chang |
| author_sort | Sehee Lee |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T13:08:42Z |
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| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T13:08:42Z |
| publishDate | 2022-12-01 |
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| spelling | doaj.art-70644c5eee3a43018b8669288bf3f3152023-11-30T21:45:12ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-12-0145128631010.3390/cimb45010021Transcriptomic Analysis of the Effect of Metformin against Cisplatin-Induced Ototoxicity: A Potential Mechanism of Metformin-Mediated Inhibition of Thioredoxin-Interacting Protein (Txnip) Gene ExpressionSehee Lee0Sun Choi1Seok Hyun Park2Gi Jung Im3Jiwon Chang4Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, Korea University College of Medicine, Seoul 02841, Republic of KoreaDepartment of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Republic of KoreaOtotoxicity 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.https://www.mdpi.com/1467-3045/45/1/21cisplatinototoxicitymetforminpreventiongene expressionTxnip pathway |
| spellingShingle | Sehee Lee Sun Choi Seok Hyun Park Gi Jung Im Jiwon Chang 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 Current Issues in Molecular Biology cisplatin ototoxicity metformin prevention gene expression Txnip pathway |
| 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 | cisplatin ototoxicity metformin prevention gene expression Txnip pathway |
| url | https://www.mdpi.com/1467-3045/45/1/21 |
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