한빛사 논문
- 조회2,258
Hepatology, Accepted manuscript online: 18 DEC 2017, DOI: 10.1002/hep.29738
Capicua suppresses hepatocellular carcinoma progression by controlling ETV4-MMP1 axis
Eunjeong Kim1, Donghyo Kim1, Jeon-Soo Lee1, Jeehyun Yoe1, Jongmin Park1, Chang-Jin Kim3, Dongjun Jeong3,4, Sanguk Kim1,2,* and Yoontae Lee1,2,*
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea
2Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea
3Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Chungnam, Republic of Korea
4Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, Cheonan, Chungnam, Republic of Korea
*Corresponding authors: Sanguk Kim, Yoontae Lee
*Corresponding authors: Sanguk Kim, Yoontae Lee
Abstract
Hepatocellular carcinoma (HCC) is developed by multiple steps accompanying progressive alterations of gene expression, which leads to increased cell proliferation and malignancy. Although environmental factors and intracellular signaling pathways that are critical for HCC progression have been identified, gene expression changes and the related genetic factors contributing to HCC pathogenesis are still insufficiently understood. In this study, we identify a transcriptional repressor Capicua/CIC as a suppressor of HCC progression and a potential therapeutic target. Expression of CIC is posttranscriptionally reduced in HCC cells. CIC levels are correlated with survival rates in patients with HCC. CIC overexpression suppresses HCC cell proliferation and invasion, whereas loss of CIC exerts opposite effects in vivo as well as in vitro. The levels of PEA3 group genes, the best-known CIC target genes, are correlated with lethality in patients with HCC. Among the PEA3 group genes, ETV4 is the most significantly upregulated gene in CIC-deficient HCC cells, consequently promoting HCC progression. Furthermore, ETV4 induces expression of MMP1, the MMP gene highly relevant to HCC progression, in HCC cells, and knockdown of MMP1 completely blocks the CIC deficiency-induced HCC cell proliferation and invasion. Conclusion: Our study demonstrates that the CIC-ETV4-MMP1 axis is a novel regulatory module controlling HCC progression. This article is protected by copyright. All rights reserved.
Keywords : Tumor suppressor; TCGA database; HCC cell proliferation; Invasion; Metastasis Abstract
Keywords : Tumor suppressor; TCGA database; HCC cell proliferation; Invasion; Metastasis Abstract
논문정보
- Research article
- 2017년 12월 (BRIC 등록일 2017-12-20)
- 국내 연구진
- 생명과학 > 세포생물학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
