circRNA basic information
circBase ID: hsa_circ_0005711
Name: hsa_circ_PIK3C3
Synonym: circPIK3C3
Host Gene: PIK3C3
Genomic location(hg19): chr18:39607406-39647477:+
Genomic location(hg38): chr18:42027442-42067513:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma
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; corresponding paracancerous tissue samples; adjacent tissues; subcutaneous tumors

Cell lines:

L02; Huh7; PLC/PRF/5; SK-HEP-1; Bel-7404; HepG2; Hep3B; QGY-7703; HEK-293 T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: SOX15, active beta-catenin, c-Myc, Wnt2b/beta-catenin pathway
Associated microRNA: miR-452-5p
Biological function: Inhibits HCC proliferation, migration, invasion, EMT, tumor stemness, tumor growth, and lenvatinib resistance; enhances apoptosis and lenvatinib sensitivity.
Molecular mechanism: circPIK3C3 acts as a ceRNA to sponge miR-452-5p, increases SOX15 expression, and suppresses the Wnt/beta-catenin pathway and c-Myc, thereby inhibiting HCC progression and lenvatinib resistance.
Biological pathway or process:

Wnt/beta-catenin (inhibits); proliferation (inhibits); migration (inhibits); invasion (inhibits); EMT (inhibits); stemness (inhibits); apoptosis (promotes); drug resistance (inhibits); ceRNA regulation (promotes)

Detected method:
Q
M
Validation methods:

Bioinformatics Analysis; RT-qPCR; Clinical Sample Validation; Cohort Study; Survival Analysis; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; TUNEL; Western Blot; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; In Vivo Animal Model; ISH (In Situ Hybridization); IHC (Immunohistochemistry)

Clinical significance:

circPIK3C3 is linked to HCC patient outcomes, higher expression predicts better prognosis, and it may serve as a prognostic biomarker and marker for forecasting lenvatinib resistance.

Description:

circPIK3C3 is a human PIK3C3-derived circRNA that is down-regulated in HCC tissues, HCC cells, and lenvatinib-resistant HCC cells. It suppresses HCC progression and lenvatinib resistance by sponging miR-452-5p, increasing SOX15 expression, and inhibiting Wnt/beta-catenin signaling. Higher circPIK3C3 expression is associated with better OS and RFS, supporting its potential as a prognostic biomarker and marker of lenvatinib response.

Confidence score:

0.8981

Other information
Title:

CircPIK3C3 inhibits hepatocellular carcinoma progression and lenvatinib resistance by suppressing the Wnt/beta-catenin pathway via the miR-452-5p/SOX15 axis.

Journal: Genomics
Published: 2025
PubMed ID: 39863187
Study type:

combined biological and clinical study

Data availability: GSE97332; Supplementary data: https://doi.org/10.1016/j.ygeno.2025.110999
Code availability: -