circRNA basic information
circBase ID: hsa_circ_0006758
Name: hsa_circ_UCK2
Synonym: circUCK2(2,3) / circRNA.1_165890204-165891322
Host Gene: UCK2
Genomic location(hg19): chr1:165859440-165860559:+
Genomic location(hg38): chr1:165890203-165891322:+
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; peritumor tissues

Cell lines:

PLC/PRF/5; SNU182; SNU398; SK-HEP-1; Hep3B; MHCC-97H; 293T

In vivo animal model:

patient-derived xenograft; cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: AGO2, CNIH4, TGFalpha, EGFR, pAKT, pERK, TFII-I
Associated microRNA: miR-149-5p
Biological function: enhances HCC proliferation, migration, and invasion; promotes tumor growth and lung metastasis; sensitizes HCC cells to EGFR inhibitors; enhances synergistic cytotoxicity of lenvatinib combined with EGFR inhibitors
Molecular mechanism: ceRNA sponge mechanism: circUCK2(2,3) sponges miR-149-5p to upregulate CNIH4, increasing TGFalpha secretion and activating EGFR with downstream pAKT and pERK signaling
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); EMT (promotes); EGFR (promotes); PI3K/AKT (promotes); ERK (promotes); ceRNA regulation (promotes)

Detected method:
Q
S
Validation methods:

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

Clinical significance:

upregulated in HCC tissues and serves as an independent risk factor for recurrence-free survival; negatively correlates with RFS and early-RFS

Description:

circUCK2(2,3) is up-regulated in HCC and promotes proliferation, migration/invasion, and metastasis. It acts as a ceRNA by sponging miR-149-5p to relieve repression of CNIH4, increasing TGFalpha secretion and activating EGFR with downstream AKT/ERK signaling. High circUCK2(2,3) predicts poorer recurrence-free survival and may indicate better response to combined lenvatinib plus EGFR inhibition.

Confidence score:

0.8996

Other information
Title:

CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFalpha-EGFR signaling.

Journal: Cellular & molecular biology letters
Published: 2025
PubMed ID: 39885395
Study type:

combined biological and clinical study

Data availability: GSE263134; GSE263915
Code availability: -