期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 7, 页码 2909-2920出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI74382
关键词
-
资金
- FIMA [RTICC-RD06 00200061]
- UTE project CIMA [RTICC-RD06 00200061]
- CIBEREhd
- Instituto de Salud Carlos III [FIS PI10/02642, FIS PI13/00359, FIS PI10/00038, FIS PI13/00385]
- Gobierno de Navarra
- Ministerio de Educacion
- Ministerio de Educacion, Cultura y Deporte, Spain
A precise equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. Maintaining this balance is particularly important for the liver, a highly differentiated organ with systemic metabolic functions that is endowed with unparalleled regenerative potential. Carcinogenesis in the liver develops as the result of hepatocellular de-differentiation and uncontrolled proliferation. Here, we identified SLU7, which encodes a pre-mRNA splicing regulator that is inhibited in hepatocarcinoma, as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Additionally, loss of SLU7 also increased hepatocellular proliferation and induced a switch to a tumor-like glycolytic phenotype. Slu7 governed the splicing and/or expression of multiple genes essential for hepatocellular differentiation, including serine/arginine-rich splicing factor 3 (Srsf3) and hepatocyte nuclear factor 4 alpha (Hnf4 alpha), and was critical for cAMP-regulated gene transcription. Together, out data indicate that SLU7 is central regulator of hepatocyte identity and quiescence.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据