circRNA basic information
circBase ID: hsa_circ_0003764
Name: hsa_circ_PTPN12
Synonym: circPTPN12 / circ-0003764
Host Gene: PTPN12
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: 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:

HCC tissues; adjacent normal liver tissues

Cell lines:

MHCC-97 H; Huh7; HepG2; HCC-LM3; Hep 3B; MHCC-97 L

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: PDLIM2, OTUD6B, P65, ESRP1
Associated microRNA: -
Biological function: Inhibits HCC cell proliferation and tumor growth; promotes apoptosis.
Molecular mechanism: circPTPN12 binds PDLIM2 (PDZ domain) and acts as a scaffold to enhance PDLIM2/OTUD6B complex formation, promoting PDLIM2 deubiquitination and facilitating PDLIM2-mediated ubiquitination/degradation of P65, thereby inhibiting NF-kappaB signaling; ESRP1 binds flanking introns/pre-PTPN12 to promote circPTPN12 biogenesis.
Biological pathway or process:

NF-kappaB (inhibits); proliferation (inhibits); apoptosis (promotes); ubiquitination (other)

Detected method:
Q
S
Validation methods:

RT-qPCR; RNA-seq; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Western Blot; IF (Immunofluorescence); In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis

Clinical significance:

Downregulation of circPTPN12 is associated with unfavorable prognosis; higher circPTPN12 levels in tumors correlate with prolonged overall survival and favorable clinicopathological features (smaller tumor size, lower TNM stage, lower Edmondson grade).

Description:

circPTPN12 is down-regulated in HCC and acts as a tumor suppressor by inhibiting proliferation and promoting apoptosis. Mechanistically, it binds PDLIM2 (PDZ domain) and scaffolds OTUD6B-PDLIM2 to maintain PDLIM2 stability, enhancing PDLIM2-mediated ubiquitination/degradation of P65 and suppressing NF-kappaB signaling; ESRP1 promotes circPTPN12 biogenesis.

Confidence score:

0.8817

Other information
Title:

ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-kappaB pathway.

Journal: Molecular cancer
Published: 2024
PubMed ID: 38992675
Study type:

combined biological and clinical study

Data availability: GSE216613; GSE14520
Code availability: -