circRNA basic information
circBase ID: hsa_circ_0000417
Name: hsa_circ_CPSF6
Synonym: circCPSF6 / circular cleavage and polyadenylation specific factor 6
Host Gene: CPSF6
Genomic location(hg19): chr12:69644908-69656342:+
Genomic location(hg38): chr12:69251128-69262562:+
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:

frozen tumor tissues; tumor tissues; matched adjacent tissues
Cell lines:

Hep3B; HepG2; HCCLM3; MHCC97H; Huh7; SNU449; PLC/PRF/5; HL-7702
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: ALKBH5, YTHDF2, PCBP2, YAP1 mRNA, YAP1, CTGF, AREG
Associated microRNA: -
Biological function: circCPSF6 promotes HCC cell proliferation, tumorigenicity, migration, invasion, EMT and tumor metastasis, while inhibiting apoptosis.
Molecular mechanism: m6A-modified circCPSF6 is regulated by ALKBH5-mediated demethylation and YTHDF2-guided decay; circCPSF6 acts as an RBP sponge for PCBP2, preventing PCBP2 binding to YAP1 mRNA and enhancing YAP1 mRNA stability, thereby activating YAP1 downstream signaling.
Biological pathway or process:

m6A modification (other); mRNA stability (promotes); Hippo/YAP (promotes); proliferation (promotes); apoptosis (inhibits); migration (promotes); invasion (promotes); metastasis (promotes); EMT (promotes)
Detected method:
Q
H
Validation methods:

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

circCPSF6 is upregulated in HCC specimens, correlated with tumor differentiation, worse OS and DFS, and elevated circCPSF6 expression is an independent prognostic marker for HCC survival.
Description:

circCPSF6 is an upregulated m6A-modified circRNA in HCC and high expression predicts worse survival. It promotes HCC proliferation, tumor growth, migration, invasion, EMT and metastasis by binding PCBP2, reducing PCBP2 interaction with YAP1 mRNA, stabilizing YAP1 and activating YAP1 downstream signaling. ALKBH5/YTHDF2-mediated m6A regulation controls circCPSF6 stability.
Confidence score:

0.9026
Other information
Title:

Activation of YAP1 by N6-Methyladenosine-Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma.

Journal: Cancer research
Published: 2022
PubMed ID: 34916222
Study type:

combined biological and clinical study
Data availability: GSE14520; GSE124535; GSE49339; Supplementary Data files
Code availability: -