Author, as appears in the article.: Fekry B; Ribas-Latre A; Baumgartner C; Deans J; Kwok C; Patel P; Fu L; Berdeaux R; Sun K; Kolonin M; Wang S; Yoo S; Sladek F; Eckel-Mahan K
Department: Medicina i Cirurgia
URV's Author/s: Ribas Latre, Aleix
Abstract: © 2018, The Author(s). Hepatocyte nuclear factor 4 alpha (HNF4α) is a master regulator of liver-specific gene expression with potent tumor suppressor activity, yet many liver tumors express HNF4α. This study reveals that P1-HNF4α, the predominant isoform expressed in the adult liver, inhibits expression of tumor promoting genes in a circadian manner. In contrast, an additional isoform of HNF4α, driven by an alternative promoter (P2-HNF4α), is induced in HNF4α-positive human hepatocellular carcinoma (HCC). P2-HNF4α represses the circadian clock gene ARNTL (BMAL1), which is robustly expressed in healthy hepatocytes, and causes nuclear to cytoplasmic re-localization of P1-HNF4α. We reveal mechanisms underlying the incompatibility of BMAL1 and P2-HNF4α in HCC, and demonstrate that forced expression of BMAL1 in HNF4α-positive HCC prevents the growth of tumors in vivo. These data suggest that manipulation of the circadian clock in HNF4α-positive HCC could be a tractable strategy to inhibit tumor growth and progression in the liver.
Thematic Areas: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Physics and astronomy (miscellaneous) Physics and astronomy (all) Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Geociências General physics and astronomy General medicine General chemistry General biochemistry,genetics and molecular biology Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência da computação Chemistry (miscellaneous) Chemistry (all) Biotecnología Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física Antropologia / arqueologia
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: aleix.ribas@urv.cat
Record's date: 2023-02-19
Papper version: info:eu-repo/semantics/publishedVersion
Papper original source: Nature Communications. 9 (1): 4349-
APA: Fekry B; Ribas-Latre A; Baumgartner C; Deans J; Kwok C; Patel P; Fu L; Berdeaux R; Sun K; Kolonin M; Wang S; Yoo S; Sladek F; Eckel-Mahan K (2018). Incompatibility of the circadian protein BMAL1 and HNF4α in hepatocellular carcinoma. Nature Communications, 9(1), 4349-. DOI: 10.1038/s41467-018-06648-6
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Entity: Universitat Rovira i Virgili
Journal publication year: 2018
Publication Type: Journal Publications
Repositori URV