TARG1 affects EGFR signaling through the regulation of RNA metabolism
Abstract Epidermal Growth Factor Receptor (EGFR) signaling plays a central role in cell proliferation, migration, and survival. Emerging evidence suggests a connection between ADP-ribosylation and EGFR regulation. Previous studies implicated PARP’s role in EGFR signaling, but the participation of AD...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-08010-5 |
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| author | Mihály Mérey Roberta Fajka-Boja Gergely Imre Péter Gudmann Zsolt Török Lajos Mátés Ágnes Czibula Gyula Timinszky |
| author_facet | Mihály Mérey Roberta Fajka-Boja Gergely Imre Péter Gudmann Zsolt Török Lajos Mátés Ágnes Czibula Gyula Timinszky |
| author_sort | Mihály Mérey |
| collection | DOAJ |
| description | Abstract Epidermal Growth Factor Receptor (EGFR) signaling plays a central role in cell proliferation, migration, and survival. Emerging evidence suggests a connection between ADP-ribosylation and EGFR regulation. Previous studies implicated PARP’s role in EGFR signaling, but the participation of ADP(ribosyl)hydrolases in it, that can revert their enzymatic modifications, still remained elusive. The role of TARG1, a macrodomain-containing hydrolase, that has been implicated in RNA metabolism, and cellular stress response, but was not studied in EGFR signaling before. Here, we investigate the impact of TARG1 depletion in U2-OS osteosarcoma cells using knockout (KO) and knockdown (KD) models. We find that TARG1 loss reduces both EGFR protein and mRNA levels. Our results show increased mRNA turnover and altered RNA distribution and translation in TARG1 KO cells, suggesting that TARG1 influences RNA metabolism and translational regulation. Notably, TARG1-deficient cells exhibit heightened sensitivity to MEK1/2 inhibition, indicating potential crosstalk between TARG1 and the Ras/MEK/ERK pathway. These findings suggest that TARG1, and possibly ADP-ribosylation, regulate EGFR expression and translation through RNA biogenesis-mediated mechanisms, highlighting its potential role in cancer cell signaling and survival. |
| format | Article |
| id | doaj-art-103aaf8dccb545f8b35f10ca70f71066 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-103aaf8dccb545f8b35f10ca70f710662025-08-20T03:37:30ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-08010-5TARG1 affects EGFR signaling through the regulation of RNA metabolismMihály Mérey0Roberta Fajka-Boja1Gergely Imre2Péter Gudmann3Zsolt Török4Lajos Mátés5Ágnes Czibula6Gyula Timinszky7Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research CentreLaboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research CentreLaboratory of Cancer Genome Research, Institute of Genetics, HUN-REN Biological Research CentreLaboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research CentreLaboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research CentreLaboratory of Cancer Genome Research, Institute of Genetics, HUN-REN Biological Research CentreLaboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research CentreLaboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research CentreAbstract Epidermal Growth Factor Receptor (EGFR) signaling plays a central role in cell proliferation, migration, and survival. Emerging evidence suggests a connection between ADP-ribosylation and EGFR regulation. Previous studies implicated PARP’s role in EGFR signaling, but the participation of ADP(ribosyl)hydrolases in it, that can revert their enzymatic modifications, still remained elusive. The role of TARG1, a macrodomain-containing hydrolase, that has been implicated in RNA metabolism, and cellular stress response, but was not studied in EGFR signaling before. Here, we investigate the impact of TARG1 depletion in U2-OS osteosarcoma cells using knockout (KO) and knockdown (KD) models. We find that TARG1 loss reduces both EGFR protein and mRNA levels. Our results show increased mRNA turnover and altered RNA distribution and translation in TARG1 KO cells, suggesting that TARG1 influences RNA metabolism and translational regulation. Notably, TARG1-deficient cells exhibit heightened sensitivity to MEK1/2 inhibition, indicating potential crosstalk between TARG1 and the Ras/MEK/ERK pathway. These findings suggest that TARG1, and possibly ADP-ribosylation, regulate EGFR expression and translation through RNA biogenesis-mediated mechanisms, highlighting its potential role in cancer cell signaling and survival.https://doi.org/10.1038/s41598-025-08010-5 |
| spellingShingle | Mihály Mérey Roberta Fajka-Boja Gergely Imre Péter Gudmann Zsolt Török Lajos Mátés Ágnes Czibula Gyula Timinszky TARG1 affects EGFR signaling through the regulation of RNA metabolism Scientific Reports |
| title | TARG1 affects EGFR signaling through the regulation of RNA metabolism |
| title_full | TARG1 affects EGFR signaling through the regulation of RNA metabolism |
| title_fullStr | TARG1 affects EGFR signaling through the regulation of RNA metabolism |
| title_full_unstemmed | TARG1 affects EGFR signaling through the regulation of RNA metabolism |
| title_short | TARG1 affects EGFR signaling through the regulation of RNA metabolism |
| title_sort | targ1 affects egfr signaling through the regulation of rna metabolism |
| url | https://doi.org/10.1038/s41598-025-08010-5 |
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