circRNA basic information
circBase ID: hsa_circ_0007444
Name: hsa_circ_RHOBTB3
Synonym: circRHOBTB3
Host Gene: RHOBTB3
Genomic location(hg19): chr5:95091099-95099324:+
Genomic location(hg38): chr5:95755395-95763620:+
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer / CRC
Disease DO ID:
5672, 9256
Disease MeSH ID:
-
Disease NCIt ID:
C4978
Disease ICD11 ID:
-
Disease OMIM ID:
114500
Species: Human
Species details: Homo sapiens
Tissue specimen:

serum exosomes; serum; colorectal carcinoma tissue; paired normal tissues; plasma; urine; spleen primary foci; liver metastatic foci

Cell lines:

RKO; HCT116; HCT8; DLD1; SW480; NCM460; HELF; THP-1; Jurkat; 293 T; LO2

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DS
Associated gene: SNF8, ENO1, ENO2
Associated microRNA: -
Biological function: Tumor-suppressive; inhibits proliferation, migration, invasion, EMT and metastasis; regulates intracellular ROS and metabolic pathways.
Molecular mechanism: circRHOBTB3 binds metabolic enzymes (ENO1/ENO2) to regulate metabolism and ROS, thereby inhibiting EMT; SNF8 (ESCRT-II) binds circRHOBTB3 and sorts it into exosomes via specific motifs (141-240 nt) enabling exosomal secretion; ASOs targeting circularization/secretion elements increase intracellular circRHOBTB3 and suppress CRC phenotypes.
Biological pathway or process:

metastasis (inhibits); EMT (inhibits); proliferation (inhibits); oxidative phosphorylation (other); oxidative phosphorylation (other); NF-kappaB (other); ERK (other); other pathway/process (other)

Detected method:
Q
S
Validation methods:

RNA-seq; RT-qPCR; divergent primers PCR; Back-Splice Junction PCR; Sanger Sequencing; RNase R Treatment; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; Bioinformatics Analysis; Transfection; RNA Pull-Down; Western Blot; RIP (RNA Immunoprecipitation); CCK8; Transwell Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Flow Cytometry(Non-apoptosis/cycle)

Clinical significance:

circRHOBTB3 is higher in CRC patient serum than healthy donors, downregulated in CRC tissues, and higher tissue expression is associated with better overall survival.

Description:

circRHOBTB3 (hsa_circ_0007444) is down-regulated in CRC tumor tissues but elevated in patient serum exosomes. Functionally, circRHOBTB3 suppresses CRC proliferation, migration/invasion, EMT and metastasis by regulating metabolism and ROS, partly through binding ENO1/ENO2, and it is sorted into exosomes via SNF8-dependent motifs; blocking its exosomal export and/or boosting its circularization with ASOs enhances antitumor effects.

Confidence score:

0.8814

Other information
Title:

Tumor-suppressive circRHOBTB3 is excreted out of cells via exosome to sustain colorectal cancer cell fitness.

Journal: Molecular cancer
Published: 2022
PubMed ID: 35148775
Study type:

combined biological and clinical study

Data availability: GSE100063; GSE100206; GSE100207; GSE100232; https://www.proteinatlas.org/about/download; 10.1186/s12943-022-01511-1
Code availability: -