2. Academic Validation
  3. Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice

Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice

  • Oncol Rep. 2023 Jul;50(1):146. doi: 10.3892/or.2023.8583.
Sojin Kim 1,  Yong Keun Song 2,  Chang Sik Cho 3,  Hyo Jung Kim 4,  Sungsoon Fang 5,  Dong Hyun Jo 4,  Hyunkyung Kim 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 02841, Republic of Korea.
  • 2 Department of Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  • 3 Fight against Angiogenesis‑Related Blindness Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea.
  • 4 Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
  • 5 Severance Biomedical Science Institute, Gangnam Severance Hospital; Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 06273, Republic of Korea.
PMID: 37326108 DOI: 10.3892/or.2023.8583
Abstract

Chemotherapies are used for treating retinoblastoma; however, numerous patients suffer from recurrence or symptoms due to chemotherapy, which emphasizes the need for alternative therapeutic strategies. The present study demonstrated that Protein Arginine Deiminase Ⅱ (PADI2) was highly expressed in human and mouse retinoblastoma tissues due to the overexpression of E2 factor (E2F). By inhibiting PADI2 activity, the expression of phosphorylated Akt was reduced, and cleaved poly (ADP‑ribose) polymerase level was increased, leading to induced Apoptosis. Similar results were obtained in orthotopic mouse models with reduced tumor volumes. In addition, BB‑Cl‑amidine showed low toxicity in vivo. These results suggested that PADI2 inhibition has potential clinical translation. Furthermore, the present study highlights the potential of epigenetic approaches to target RB1‑deficient mutations at the molecular level. The current findings provide new insights into the importance of retinoblastoma intervention by managing PADI2 activity according to the treatment of specific inhibitors and depletion approaches in vitro and in orthotopic mouse models.

Keywords

AKT phosphorylation; BB‑Cl‑amidine; E2 factor; protein arginine deiminase II; retinoblastoma.

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