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| Status |
Public on May 29, 2014 |
| Title |
Slu7 is essential for liver differentiation, metabolism and quiescence |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. This is particularly important for the liver, a highly differentiated organ with systemic metabolic functions still endowed with unparalleled regenerative potential. Hepatocellular de-differentiation and uncontrolled proliferation are at the basis of liver carcinogenesis. We have identified SLU7, a pre-mRNA splicing regulator 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. Hepatocellular proliferation and a switch to a tumor-like glycolytic phenotype were also observed. Mechanistically, SLU7 governed the splicing and/or expression of essential genes for hepatocellular differentiation like SRSF3 and HNF4a, and was identified as a critical factor in cAMP-regulated gene transcription. SLU7 is therefore central for hepatocyte identity and quiescence.
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| Overall design |
The expression of the splicing factor SLU7 in the human hepatocellular carcinoma cell line PLC/PRF/5 was knocked down with specific siRNAs (siSlu7). An irrelevant siRNA (siGL2) was used as negative control. The RNAto perfrom the array analysis was extracted 48h after transfection.
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| Contributor(s) |
Elizalde M, Segura V, Prieto J, Avila M, Berasain C |
| Citation(s) |
24865429 |
| Submission date |
Jan 15, 2014 |
| Last update date |
Jul 10, 2014 |
| Contact name |
Victor Segura |
| E-mail(s) |
vsegura@unav.es
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| Organization name |
FIMA
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| Department |
Unit of Proteomics, Genomics and Bioinformatics
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| Street address |
Avda. Pío XII, 55
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| City |
Pamplona |
| State/province |
Navarra |
| ZIP/Postal code |
31008 |
| Country |
Spain |
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| Platforms (1) |
| GPL5188 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA235169 |
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