2. Academic Validation
  3. TARG1 affects EGFR signaling through the regulation of RNA metabolism

TARG1 affects EGFR signaling through the regulation of RNA metabolism

  • Sci Rep. 2025 Jul 2;15(1):23651. doi: 10.1038/s41598-025-08010-5.
Mihály Mérey 1 2,  Roberta Fajka-Boja 1 3,  Gergely Imre 4 5,  Péter Gudmann 6,  Zsolt Török 6,  Lajos Mátés 4,  Ágnes Czibula 7 8,  Gyula Timinszky 9
Affiliations

Affiliations

  • 1 Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, 6726, Hungary.
  • 2 Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, 6720, Hungary.
  • 3 Department of Immunology, University of Szeged, Szeged, 6720, Hungary.
  • 4 Laboratory of Cancer Genome Research, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, 6726, Hungary.
  • 5 Doctoral School of Biology, University of Szeged, Szeged, 6720, Hungary.
  • 6 Laboratory of Molecular Stress Biology, Institute of Biochemistry, HUN-REN Biological Research Centre, Szeged, 6726, Hungary.
  • 7 Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, 6726, Hungary. czibula.agnes@brc.hu.
  • 8 Department of Immunology, University of Szeged, Szeged, 6720, Hungary. czibula.agnes@brc.hu.
  • 9 Laboratory of DNA Damage and Nuclear Dynamics, Institute of Genetics, HUN-REN Biological Research Centre, Szeged, 6726, Hungary. timinszky.gyula@brc.hu.
PMID: 40603466 DOI: 10.1038/s41598-025-08010-5
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.

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