한빛사논문
- 조회587
Seung Min Lee1, Jeongin Cho1, Sujin Choi1, Dong Ha Kim1, Je‑Won Ryu2, Inki Kim5, Dong‑Cheol Woo4, Young Hoon Sung3, Jin‑Yong Jeong6, In‑Jeoung Baek3, Chan‑Gi Pack4, Jin Kyung Rho1, Sang‑wook Lee2* and Chang Hoon Ha1,7*
1Department of Biochemistry and Molecular Biology and Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic‑Ro 43‑Gil, Songpa‑Gu, Seoul 05505, Republic of Korea.
2Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic‑Ro 43‑Gil, Songpa‑Gu, Seoul 05505, Republic of Korea.
3Department of Cell and Genetic Engineering, Asan Medical Center, Asan Institute for Life Sciences University of Ulsan College of Medicine, Seoul, Republic of Korea.
4Department of Biomedical Engineering, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
5Department of Pharmacology, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
6Department of Microbiology, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Republic of Korea.
7Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Corresponding authors : Correspondence to Sang-wook Lee or Chang Hoon Ha.
Abstract
Background: Tumor-derived exosomes are critical elements of the cell-cell communication response to various stimuli. This study aims to reveal that the histone deacetylase 5 (HDAC5) and p53 interaction upon radiation in hepatocellular carcinoma intricately regulates the secretion and composition of exosomes.
Methods: We observed that HDAC5 and p53 expression were significantly increased by 2 Gy and 4 Gy radiation exposure in HCC. Normal- and radiation-derived exosomes released by HepG2 were purified to investigate the exosomal components.
Results: We found that in the radiation-derived exosome, exosomal Maspin was notably increased. Maspin is known as an anti-angiogenic gene. The expression of Maspin was regulated at the cellular level by HDAC5, and it was elaborately regulated and released in the exosome. Radiation-derived exosome treatment caused significant inhibition of angiogenesis in HUVECs and mouse aortic tissues. Meanwhile, we confirmed that miR-151a-3p was significantly reduced in the radiation-derived exosome through exosomal miRNA sequencing, and three HCC-specific exosomal miRNAs were also decreased. In particular, miR-151a-3p induced an anti-apoptotic response by inhibiting p53, and it was shown to induce EMT and promote tumor growth by regulating p53-related tumor progression genes. In the HCC xenograft model, radiation-induced exosome injection significantly reduced angiogenesis and tumor size.
Conclusions: Our present findings demonstrated HDAC5 is a vital gene of the p53-mediated release of exosomes resulting in tumor suppression through anti-cancer exosomal components in response to radiation. Finally, we highlight the important role of exosomal Maspin and mi-151a-3p as a biomarker in enhancing radiation treatment sensitivity. Therapeutic potential of HDAC5 through p53-mediated exosome modulation in radiation treatment of hepatocellular carcinoma.
논문정보
- Research article
- 2023년 12월 (BRIC 등록일 2023-12-18)
- 국내 연구진
- 생명과학 > 세포생물학
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