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Exp. Mol. Med., Dec 02 2024, | https://doi.org/10.1038/s12276-024-01352-6
VIM-AS1, which is regulated by CpG methylation, cooperates with IGF2BP1 to inhibit tumor aggressiveness via EPHA3 degradation in hepatocellular carcinoma
Su-hyang Han1,5, Je Yeong Ko2,5, Sungju Jung1, Sumin Oh1, Do Yeon Kim2, Eunseo Kang1, Myung Sup Kim3, Kyung-Hee Chun3, Kyung Hyun Yoo1,4 and Jong Hoon Park2
1Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
2Molecular Medicine Laboratory, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
3Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
4Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
5These authors contributed equally: Su-hyang Han, Je Yeong Ko.
Corresponding authors
Correspondence to Kyung Hyun Yoo or Jong Hoon Park.
1Laboratory of Biomedical Genomics, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
2Molecular Medicine Laboratory, Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
3Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea.
4Research Institute of Women’s Health, Sookmyung Women’s University, Seoul 04310, Republic of Korea.
5These authors contributed equally: Su-hyang Han, Je Yeong Ko.
Corresponding authors
Correspondence to Kyung Hyun Yoo or Jong Hoon Park.
Abstract
Early tumor recurrence in hepatocellular carcinoma (HCC) remains a challenging area, as the mechanisms involved are not fully understood. While microvascular invasion is linked to early recurrence, established biomarkers for diagnosis and prognostication are lacking. In this study, our objective was to identify DNA methylation sites that can predict the outcomes of liver cancer patients and elucidate the molecular mechanisms driving HCC aggressiveness. Using DNA methylome data from HCC patient samples from the CGRC and TCGA databases, we pinpointed hypermethylated CpG sites in HCC. Our analysis revealed that cg02746869 acts as a crucial regulatory site for VIM-AS1 (vimentin antisense RNA1), a 1.8 kb long noncoding RNA. RNA sequencing of HCC cells with manipulated VIM-AS1 expression revealed EPHA3 as a pathogenic target of VIM-AS1, which performs an oncogenic function in HCC. Hypermethylation-induced suppression of VIM-AS1 significantly impacted HCC cell dynamics, particularly impairing motility and invasiveness. Mechanistically, reduced VIM-AS1 expression stabilized EPHA3 mRNA by enhancing the binding of IGF2BP1 to EPHA3 mRNA, leading to increased expression of EPHA3 mRNA and the promotion of HCC progression. In vivo experiments further confirmed that the VIM-AS1‒EPHA3 axis controlled tumor growth and the tumor microenvironment in HCC. These findings suggest that the downregulation of VIM-AS1 due to hypermethylation at cg02746869 increased EPHA3 mRNA expression via a m6A-dependent mechanism to increase HCC aggressiveness.
논문정보
- Research article
- 2024년 12월 (BRIC 등록일 2024-12-04)
- 국내 연구진
- 생명과학 > 유전학
관련 보도자료
간암의 조기 재발 원인 찾았다
숙명여자대학교 생명시스템학부 유경현 교수와 박종훈 연구특임교수 연구팀이 간세포암(HCC) 조기 재발의 원인을 밝혀내고, 이를 진단하고 치료할 새로운 가능성을 제시하는 연구 결과를 발표했다. 연구팀에 따르면 간세포암은 전 세계적으로 주요한 암 관련 사망 원인 중 하나로, 치료 후에도 재발률이 높다는 점이 문제로 지적돼왔다. 미세혈관 침윤이 조기 재발과 연관된 것으로 알려졌지만, 이를 조기에 진단하거나 예후를 예측할 수 있는 신뢰성 높은 바이오마커는 아직 부족한 상황이다.
- Bio통신원
- 2024. 12. 09
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