circRNA basic information
circBase ID: hsa_circ_0087293
Name: hsa_circ_TLE4
Synonym: -
Host Gene: TLE4
Genomic location(hg19): chr9:82267504-82268990:+
Genomic location(hg38): chr9:79652589-79654075:+
Subcellular localization: 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 tumor tissues

Cell lines:

HepG2-SR; SKhep1-SR; Huh7-SR; LM3-SR; HepG2; SKhep1; Huh7; LM3; 293 T

In vivo animal model:

patient-derived xenograft / cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: Wnt2b, beta-catenin, METTL3, FTO, YTHDF1/2
Associated microRNA: miR-103a-2-5p, miR-660-3p
Biological function: sustains sorafenib resistance and inhibits sorafenib-induced apoptosis
Molecular mechanism: Acts as a miRNA sponge (ceRNA) for miR-103a-2-5p and miR-660-3p to activate Wnt2b/beta-catenin signaling; m6A modification increases circRNA-SORE stability.
Biological pathway or process:

Wnt/beta-catenin (promotes); apoptosis (inhibits); chemoresistance (promotes); m6A modification (promotes)

Detected method:
Q
Validation methods:

RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Actinomycin D / DRB Stability Assay; Transfection; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Western Blot; CCK8; Colony Formation Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis

Clinical significance:

Lower circRNA-SORE expression is associated with better recurrence free survival and overall survival in HCC patients (including sorafenib-treated cohort).

Description:

circRNA-SORE is up-regulated in sorafenib-resistant HCC and is required to maintain resistance by suppressing sorafenib-induced apoptosis. It acts as a ceRNA that sponges miR-103a-2-5p and miR-660-3p, thereby activating Wnt2b/beta-catenin signaling. Its elevated abundance in resistant cells is promoted by m6A-dependent stabilization, and targeting it in vivo enhances sorafenib efficacy.

Confidence score:

0.8729

Other information
Title:

N6-methyladenosine-modified CircRNA-SORE sustains sorafenib resistance in hepatocellular carcinoma by regulating beta-catenin signaling.

Journal: Molecular cancer
Published: 2020
PubMed ID: 33222692
Study type:

combined biological and clinical study

Data availability: Supplementary material available at 10.1186/s12943-020-01281-8
Code availability: -