circRNA basic information
circBase ID: hsa_circ_0078619
Name: hsa_circ_MAP3K4
Synonym: circMAP3K4
Host Gene: MAP3K4
Genomic location(hg19): chr6:161469647-161471011:+
Genomic location(hg38): chr6:161048615-161049979:+
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 liver tissues / non-neoplastic liver tissues

Cell lines:

Huh7; HEK293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP1, IGF2BP2, AIF, MIB1, METTL3, ALKBH5, FTO
Associated microRNA: -
Biological function: promotes HCC cell growth and prevents cisplatin-induced apoptosis, contributing to chemoresistance
Molecular mechanism: m6A modification enables IGF2BP1-mediated translation of circMAP3K4 into circMAP3K4-455aa; the peptide binds AIF to inhibit AIF cleavage and nuclear translocation; circMAP3K4-455aa is ubiquitinated by MIB1 and degraded via the proteasome
Biological pathway or process:

apoptosis (inhibits); chemoresistance (promotes); proliferation (promotes); ubiquitination (other); m6A modification (promotes)

Detected method:
Q
B
H
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Northern Blot; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; ROC Analysis; Survival Analysis; Cohort Study; Bioinformatics Analysis; Transfection; CCK8; Annexin V/PI Flow Cytometry; TUNEL; Western Blot; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; MeRIP / MeRIP-seq; RNA-seq; In Vivo Animal Model; H&E Staining; IF (Immunofluorescence); Co-IP

Clinical significance:

High circMAP3K4 level is an independent prognostic factor for adverse overall survival and adverse disease-free survival in HCC patients

Description:

circMAP3K4 is upregulated in HCC and serves as an adverse prognostic factor. Via m6A modification, IGF2BP1 promotes translation of circMAP3K4 into the peptide circMAP3K4-455aa, which binds AIF to reduce AIF cleavage and nuclear translocation, thereby suppressing cisplatin-induced apoptosis and contributing to chemoresistance; the peptide is ubiquitinated by MIB1 for proteasomal degradation.

Confidence score:

0.904

Other information
Title:

A novel peptide encoded by N6-methyladenosine modified circMAP3K4 prevents apoptosis in hepatocellular carcinoma.

Journal: Molecular cancer
Published: 2022
PubMed ID: 35366894
Study type:

combined biological and clinical study

Data availability: The datasets sharing is available from the corresponding author Mu-Yan Cai on reasonable request.
Code availability: -