circRNA basic information
circBase ID: -
Name: hsa_circ_LPAR1
Synonym: circLPAR1 / CircRNA lysophosphatidic acid receptor 1
Host Gene: LPAR1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: not tested
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0004975
MONDO name: Alzheimer disease
Disease details: Alzheimer's disease / AD
Disease DO ID:
10652
Disease MeSH ID:
D000544
Disease NCIt ID:
C2866
Disease ICD11 ID:
1611724421
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

mouse brain tissues; hippocampus; brain tissues

Cell lines:

SH-SY5Y

In vivo animal model:

genetically engineered animal model

circRNA-disease information
Expression pattern:
UP
Associated gene: UPF1, GDF-15 mRNA, GDF-15, SIRT1, Nrf-2, HO-1
Associated microRNA: -
Biological function: Promotes Abeta-induced neuroinflammation, oxidative stress, neuronal apoptosis, AD-related pathological traits, and cognitive dysfunction; circLPAR1 knockdown protects SH-SY5Y cells and improves AD-related pathology in APP/PS1 mice.
Molecular mechanism: circLPAR1 recruits the RNA-binding protein UPF1, decreases GDF-15 mRNA stability, represses GDF-15 expression, and thereby inhibits the GDF-15/SIRT1/Nrf-2/HO-1 axis in AD models.
Biological pathway or process:

inflammation (promotes); apoptosis (promotes); mRNA stability (inhibits); other pathway/process (other)

Detected method:
Q
Validation methods:

RT-qPCR; Transfection; CCK8; Annexin V/PI Flow Cytometry; TUNEL; ELISA; Western Blot; RIP (RNA Immunoprecipitation); RNA Pull-Down; Actinomycin D / DRB Stability Assay; In Vivo Animal Model; H&E Staining; Bioinformatics Analysis

Clinical significance:

-

Description:

circLPAR1 is up-regulated in APP/PS1 mouse brain and Abeta-treated SH-SY5Y cells. It promotes AD-like neuronal injury, neuroinflammation, oxidative stress, and apoptosis by recruiting UPF1 to destabilize GDF-15 mRNA, suppressing the GDF-15/SIRT1/Nrf-2/HO-1 protective axis. Silencing circLPAR1 alleviates cellular injury and improves cognitive/pathological phenotypes in APP/PS1 mice.

Confidence score:

0.6966

Other information
Title:

CircLPAR1 Promotes Neuroinflammation and Oxidative Stress in APP/PS1 Mice by Inhibiting SIRT1/Nrf-2/HO-1 Axis Through Destabilizing GDF-15 mRNA.

Journal: Molecular neurobiology
Published: 2023
PubMed ID: 36646968
Study type:

biological research

Data availability: All data generated or analyzed during this study are included in this published article.
Code availability: -