Back to Search
Start Over
A Liver-Specific Long Noncoding RNA With a Role in Cell Viability Is Elevated in Human Nonalcoholic Steatohepatitis
- Source :
- Hepatology, 66(3), 794-808. Wiley
- Publication Year :
- 2017
-
Abstract
- Hepatocyte apoptosis in nonalcoholic steatohepatitis (NASH) can lead to fibrosis and cirrhosis, which permanently damage the liver. Understanding the regulation of hepatocyte apoptosis is therefore important to identify therapeutic targets that may prevent the progression of NASH to fibrosis. Recently, increasing evidence has shown that long noncoding (lnc) RNAs are involved in various biological processes and that their dysregulation underlies a number of complex human diseases. By performing gene expression profiling of 4,383 lncRNAs in 82 liver samples from individuals with NASH (n = 48), simple steatosis but no NASH (n = 11), and healthy controls (n = 23), we discovered a liver-specific lncRNA (RP11-484N16.1) on chromosome 18 that showed significantly elevated expression in the liver tissue of NASH patients. This lncRNA, which we named lnc18q22.2 based on its chromosomal location, correlated with NASH grade (r = 0.51, P = 8.11 × 10-7 ), lobular inflammation (r = 0.49, P = 2.35 × 10-6 ), and nonalcoholic fatty liver disease activity score (r = 0.48, P = 4.69 × 10-6 ). The association of lnc18q22.2 to liver steatosis and steatohepatitis was replicated in 44 independent liver biopsies (r = 0.47, P = 0.0013). We provided a genetic structure of lnc18q22.2 showing an extended exon 2 in liver. Knockdown of lnc18q22.2 in four different hepatocyte cell lines resulted in severe phenotypes ranging from reduced cell growth to lethality. This observation was consistent with pathway analyses of genes coexpressed with lnc18q22.2 in human liver or affected by lnc18q22.2 knockdown. Conclusion We identified an lncRNA that can play an important regulatory role in liver function and provide new insights into the regulation of hepatocyte viability in NASH. (Hepatology 2017;66:794-808).
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Cirrhosis
Cell Survival
HEPATIC GENE-EXPRESSION
FEATURES
PROTEIN
Apoptosis
Biology
Risk Assessment
Sampling Studies
DISEASE
03 medical and health sciences
0302 clinical medicine
Non-alcoholic Fatty Liver Disease
Fibrosis
HEPATOCYTE APOPTOSIS
Internal medicine
Nonalcoholic fatty liver disease
medicine
Humans
Cells, Cultured
Gene knockdown
Hepatology
Biopsy, Needle
Microarray Analysis
medicine.disease
Immunohistochemistry
3. Good health
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
Hepatocyte
OBESITY
Immunology
Disease Progression
Hepatocytes
Cancer research
Female
RNA, Long Noncoding
Liver function
Steatohepatitis
DECAY
Subjects
Details
- Language :
- English
- ISSN :
- 02709139
- Volume :
- 66
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Hepatology
- Accession number :
- edsair.doi.dedup.....4d6e7657cf9c2eb5fd67c1828e8248c6