circRNA basic information
circBase ID: -
Name: hsa_circ_PRKAA1
Synonym: circPRKAA1 / hsa_circ_000955
Host Gene: PRKAA1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma / HCC
Disease DO ID:
 684, 686
Disease MeSH ID:
 D006528
Disease NCIt ID:
 C3099
Disease ICD11 ID:
 1294035808
Disease OMIM ID:
 114550
Species: Human
Species details: Homo sapiens
Tissue specimen:

hepatocellular carcinoma tissue; para-cancerous normal tissues; adjacent normal tissue; HCC tumor samples
Cell lines:

HCT116; HepG2; PLC/PRF/5; Huh7; HCCLM3; Hep3B; SK-Hep-1; SMMC-7721; HAFF; WRL68; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: Ku80, Ku70, mSREBP-1, SREBP-1, ACC1, ACLY, SCD1, FASN, SRSF1, AMPK, FBXW7
Associated microRNA: -
Biological function: Promotes de novo fatty acid synthesis, lipid accumulation, lipid droplet formation, triglyceride storage, tumor cell proliferation, clonogenic growth, and xenograft tumor growth in hepatocellular carcinoma cells.
Molecular mechanism: circPRKAA1 directly binds Ku80/Ku70, facilitates formation of a circPRKAA1/Ku80/Ku70/mSREBP-1 tetrameric complex, stabilizes mSREBP-1 by preventing proteasomal degradation, and binds promoters of SREBP-1 target genes to enhance transcription of ACC1, ACLY, SCD1, and FASN. Its biogenesis is induced by low AMPK activity through SRSF1-dependent back-splicing.
Biological pathway or process:

lipid metabolism (promotes); proliferation (promotes); ubiquitination (inhibits); other pathway/process (promotes)
Detected method:
Q
B
H
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Northern Blot; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; Colony Formation Assay; In Vivo Animal Model; Western Blot; Bioinformatics Analysis; RNA-seq; Digital PCR
Clinical significance:

circPRKAA1 is commonly upregulated in HCC tissue and negatively correlated with p-AMPK levels; targeting circPRKAA1 could offer new therapeutic opportunities for HCC.
Description:

circPRKAA1 is an upregulated PRKAA1-derived circRNA in hepatocellular carcinoma. It promotes HCC cell lipogenesis and tumor growth by binding Ku80/Ku70, stabilizing mSREBP-1, and recruiting mSREBP-1 to fatty-acid-synthesis gene promoters including ACC1, ACLY, SCD1, and FASN. Low AMPK activity promotes circPRKAA1 biogenesis through SRSF1-dependent splicing, and high circPRKAA1 expression is negatively correlated with p-AMPK in HCC tissues.
Confidence score:

0.8882
Other information
Title:

circPRKAA1 activates a Ku80/Ku70/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells.

Journal: Cell reports
Published: 2022
PubMed ID: 36417875
Study type:

combined biological and clinical study
Data availability: GSE201844; https://doi.org/10.17632/f77brpmvhc.2; Supplemental information can be found online at https://doi.org/10.1016/j. celrep.2022.111707; Table S1
Code availability: -