circRNA basic information
circBase ID: hsa_circ_0001134
Name: hsa_circ_XRN2
Synonym: circXRN2
Host Gene: XRN2
Genomic location(hg19): chr20:21319681-21324846:+
Genomic location(hg38): chr20:21339043-21344208:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0004986
MONDO name: urinary bladder carcinoma
Disease details: bladder cancer / BCa
Disease DO ID:
4007
Disease MeSH ID:
-
Disease NCIt ID:
C4912
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

bladder cancer tissues; adjacent normal tissues; surgical tissue samples

Cell lines:

SV-HUC-1; 5637; T24; EJ; TCCSUP; UM-UC-3; 293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: LATS1, SPOP, TAZ, YAP, H3K18la, LCN2
Associated microRNA: -
Biological function: Inhibits proliferation and migration, promotes apoptosis, suppresses glycolysis and lactate production, and suppresses tumor growth and metastasis in bladder cancer.
Molecular mechanism: circXRN2 binds LATS1 at the SPOP-binding degron to prevent SPOP-mediated ubiquitination and degradation of LATS1, stabilizing LATS1 and activating Hippo signaling (TAZ/YAP cytoplasmic retention), which suppresses glycolysis/lactate and inhibits H3K18 lactylation-driven LCN2 transcription.
Biological pathway or process:

Hippo/YAP (promotes); proliferation (inhibits); migration (inhibits); apoptosis (promotes); glycolysis (inhibits)

Detected method:
Q
S
Validation methods:

circRNA-seq; RIP (RNA Immunoprecipitation); RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; FISH / smFISH; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; Co-IP; Western Blot; IF (Immunofluorescence); Flow Cytometry(Non-apoptosis/cycle)

Clinical significance:

-

Description:

circXRN2 (hsa_circ_0001134) is down-regulated in human bladder cancer and suppresses tumor proliferation, migration, and in vivo growth/metastasis while reducing glycolysis and lactate production. Mechanistically, it binds LATS1 at the SPOP-binding degron to prevent SPOP-mediated ubiquitination/degradation, activates Hippo signaling (TAZ/YAP inhibition), and thereby reduces H3K18 lactylation and LCN2 expression.

Confidence score:

0.7752

Other information
Title:

CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer.

Journal: Molecular cancer
Published: 2023
PubMed ID: 37684641
Study type:

combined biological and clinical study

Data availability: Supplementary file 1; Supplementary File 2; Supplementary files 3; Supplementary files 4 and 5; Supplementary files 6 and 7; 10.1186/s12943-023-01856-1
Code availability: -