circRNA basic information
circBase ID: hsa_circ_0058497
Name: hsa_circ_RHBDD1
Synonym: circRHBDD1
Host Gene: RHBDD1
Genomic location(hg19): chr2:227771508-227779067:+
Genomic location(hg38): chr2:226906792-226914351:+
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 / adjacent liver tissues; engrafted tumors (PDX); tumor tissues

Cell lines:

HCCLM3; MHCC97H; HepG2; Huh7; Hepa1-6; QSG-7701

In vivo animal model:

patient-derived xenograft; cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: YTHDF1, PIK3R1, EIF4A3, GLUT1, HK2, PI3K/AKT
Associated microRNA: -
Biological function: promotes HCC cell proliferation and aerobic glycolysis; promotes tumor growth; restricts anti-PD-1 therapy efficacy
Molecular mechanism: circRHBDD1 acts as a scaffold recruiting the m6A reader YTHDF1 to PIK3R1 mRNA to enhance PIK3R1 translation in an m6A-dependent manner; EIF4A3 promotes circRHBDD1 biogenesis via exon back-splicing; activation of PI3K/AKT signaling
Biological pathway or process:

glycolysis (promotes); proliferation (promotes); PI3K/AKT (promotes); m6A modification (promotes)

Detected method:
Q
S
Validation methods:

circRNA-seq; RT-qPCR; RNase R Treatment; Sanger Sequencing; divergent primers PCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Actinomycin D / DRB Stability Assay; RNA-seq; Clinical Sample Validation; Survival Analysis; Transfection; RIP (RNA Immunoprecipitation); CLIP; RNA Pull-Down; Western Blot; Luciferase Reporter Assay; MeRIP / MeRIP-seq; CCK8; EdU Staining; Colony Formation Assay; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); Bioinformatics Analysis

Clinical significance:

high circRHBDD1 expression was correlated with poor overall survival and disease-free survival; circRHBDD1 level was an independent prognostic factor for overall survival and disease-free survival

Description:

circRHBDD1 is up-regulated in HCC and promotes proliferation and glycolysis. It acts as a scaffold to recruit YTHDF1 to PIK3R1 mRNA, enhancing m6A-dependent translation of PIK3R1 and activating PI3K/AKT signaling, thereby promoting tumor growth and reducing anti-PD-1 therapy efficacy.

Confidence score:

0.9002

Other information
Title:

CircRHBDD1 augments metabolic rewiring and restricts immunotherapy efficacy via m6A modification in hepatocellular carcinoma.

Journal: Molecular therapy oncolytics
Published: 2022
PubMed ID: 35317519
Study type:

combined biological and clinical study

Data availability: GEO: GSE78030; GEO: GSE63591; GEO: GSE122744; https://doi.org/10.1016/j.omto.2022.02.021
Code availability: -