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LncRNA H19/microRNA-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by hepatitis B X protein via Akt/mTOR signalling
- Source :
- Molecular immunology. 116
- Publication Year :
- 2019
-
Abstract
- Emerging evidence indicates that the lncRNAs/microRNA/mRNA axis plays important roles in a variety of diseases. This study was aimed to investigate the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating hepatitis B virus (HBV)-associated liver injury. mRNA and miR-675 levels were determined by quantitative real-time PCR (qRT-PCR), protein levels were determined by western blot, cell viability was measured by the MTT assay, cell apoptosis was measured by flow cytometry, inflammatory cytokine production was determined by ELISA, oxidative stress and energy metabolism were assessed by commercial kits, and the target relationship between PPARα and miR-675 was confirmed by the dual-luciferase reporter assay. The results showed that the expression of lncRNA H19 and miR-675 was up-regulated in patients with chronic hepatitis B (n = 20). Inhibition of lncRNA H19 or miR-675 in L02 cells increased cell viability, suppressed hepatitis B X protein (HBx)-induced cell apoptosis, inflammatory cytokine production, and oxidative stress, and remodelled energy metabolism. Furthermore, PPARα was found to be a target gene of miR-675. The expression of PPARα was down-regulated in patients with chronic hepatitis B, and there was a negative correlation between the expression of lncRNA H19 and PPARα, or between miR-675 and PPARα. Moreover, by knocking down the expression of PPARα, the actions (apoptosis, inflammatory factors, oxidative stress, and energy metabolism) of lncRNA H19 or miR-675 inhibition in HBx-induced L02 cells were at least partially reversed. In addition, HBx-induced elevated levels of p-AktSer473, p-AktThr308 and p-mTORSer2448 were down-regulated by lncRNA H19 or miR-675 inhibition. Furthermore, PPARα knockdown partly reversed the down-regulated effects of H19 or miR-675 inhibition. Taken together, these data indicate that the lncRNA H19/miR-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by HBx, which may be related to the modulation of Akt/mTOR signalling.
- Subjects :
- 0301 basic medicine
Hepatitis B virus
Cell Survival
medicine.medical_treatment
Immunology
Down-Regulation
Apoptosis
Cell Line
03 medical and health sciences
0302 clinical medicine
microRNA
medicine
Humans
PPAR alpha
Viral Regulatory and Accessory Proteins
Viability assay
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
Chemistry
Liver cell
TOR Serine-Threonine Kinases
Hepatitis B
Cell biology
HBx
MicroRNAs
030104 developmental biology
Cytokine
HEK293 Cells
Liver
Trans-Activators
RNA, Long Noncoding
Energy Metabolism
Proto-Oncogene Proteins c-akt
030215 immunology
Signal Transduction
Subjects
Details
- ISSN :
- 18729142
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Molecular immunology
- Accession number :
- edsair.doi.dedup.....039c76196c99f21ac231be10e8c5d189