Back to Search
Start Over
A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C
- Source :
- RNA Biol
- Publication Year :
- 2020
- Publisher :
- Informa UK Limited, 2020.
-
Abstract
- Imbalance in lipid metabolism induces steatosis in liver during Chronic hepatitis C (CHC). Contribution of microRNAs in regulating lipid homoeostasis and liver disease progression is well established using small RNA-transcriptome data. Owing to the complexity in the development of liver diseases, the existence and functional importance of yet undiscovered regulatory miRNAs in disease pathogenesis was explored in this study using the unmapped sequences of the transcriptome data of HCV-HCC liver tissues following miRDeep2.pl pipeline. MicroRNA-c12 derived from the first intron of LGR5 of chromosome 12 was identified as one of the miRNA like sequences retrieved in this analysis that showed human specific origin. Northern blot hybridization has proved its existence in the hepatic cell line. Enrichment of premiR-c12 in dicer-deficient cells and miR-c12 in Ago2-RISC complex clearly suggested that it followed canonical miRNA biogenesis pathway and accomplished its regulatory function. Expression of this miRNA was quite low in CHC tissues than normal liver implying HCV-proteins might be regulating its biogenesis. Promoter scanning and ChIP analysis further revealed that under expression of p53 and hyper-methylation of STAT3 binding site upon HCV infection restricted its expression in CHC tissues. Centrosomal protein 350 (CEP350), which sequestered PPARα, was identified as one of the targets of miR-c12 using Miranda and validated by luciferase assay/western blot analysis. Furthermore, reduced triglyceride accumulation and enhanced PPARα mediated transcription of β-oxidation genes upon restoration of miR-c12 in liver cells suggested its role in lipid catabolism. Thus this study is reporting miR-c12 for the first time and showed its' protective role during chronic HCV infection.
- Subjects :
- Hepatitis C virus
Hepacivirus
Biology
medicine.disease_cause
Severity of Illness Index
Cell Line
03 medical and health sciences
Liver disease
0302 clinical medicine
Chronic hepatitis
microRNA
medicine
Humans
PPAR alpha
Promoter Regions, Genetic
Molecular Biology
030304 developmental biology
0303 health sciences
Fatty Acids
Nuclear Proteins
Correction
Lipid metabolism
Cell Biology
Hepatitis C, Chronic
Lipid Metabolism
medicine.disease
MicroRNAs
CEP350
Gene Expression Regulation
Liver
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Microtubule Proteins
Cancer research
Nucleic Acid Conformation
RNA Interference
lipids (amino acids, peptides, and proteins)
Steatosis
Oxidation-Reduction
Homeostasis
Protein Binding
Research Paper
Subjects
Details
- ISSN :
- 15558584 and 15476286
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- RNA Biology
- Accession number :
- edsair.doi.dedup.....72d40e9afbb922aaebdb441d4bcfea13