circRNA basic information
circBase ID: hsa_circ_0004183
Name: hsa_circ_FRMD4A
Synonym: circFRMD4A
Host Gene: FRMD4A
Genomic location(hg19): chr10:13701322-13717044:-
Genomic location(hg38): chr10:13659322-13675044:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer
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:

colorectal cancer tissues; matched normal tissues; breast cancer tissues; adjacent normal tissues
Cell lines:

CAL51; HCT116; A549; RKO; MCF-7; SW620; MDA-MB-231; H1975; ES-2; HCT116 p53-/-; H1299; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: PKM2, EWSR1, p53, FRMD4A
Associated microRNA: -
Biological function: Suppresses tumor growth and progression, inhibits cancer cell proliferation, colony formation, migration and invasion, promotes apoptosis, and sensitizes colorectal and breast cancer cells to elesclomol-induced cuproptosis.
Molecular mechanism: p53 transcriptionally activates FRMD4A to increase circFRMD4A, EWSR1 facilitates circFRMD4A biogenesis, and circFRMD4A directly binds PKM2 to inhibit PKM2 tetramerization and activity, reducing glycolysis and redirecting glycolytic flux toward the TCA cycle, thereby promoting mitochondrial metabolism and cuproptosis sensitivity.
Biological pathway or process:

proliferation (inhibits); apoptosis (promotes); migration (inhibits); invasion (inhibits); metastasis (inhibits); glycolysis (inhibits); mitochondrial function (promotes); other pathway/process (promotes); drug resistance (inhibits)
Detected method:
Q
H
M
Validation methods:

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

Lower circFRMD4A expression correlated with advanced T stage and lymph node metastasis and predicted worse overall survival in colorectal cancer; higher circFRMD4A expression was associated with a better prognosis.
Description:

circFRMD4A is a human FRMD4A-derived circRNA down-regulated in colorectal and breast cancer and functions as a tumor suppressor. p53 induces FRMD4A/circFRMD4A expression, while EWSR1 facilitates circFRMD4A biogenesis; circFRMD4A binds PKM2, inhibits PKM2 tetramerization and glycolysis, redirects glycolytic flux toward the TCA cycle, and sensitizes cancer cells to elesclomol-induced cuproptosis. Clinically, higher circFRMD4A expression is associated with better prognosis in colorectal cancer.
Confidence score:

0.9032
Other information
Title:

p53 induces circFRMD4A to suppress cancer development through glycolytic reprogramming and cuproptosis.

Journal: Molecular cell
Published: 2025
PubMed ID: 39637854
Study type:

combined biological and clinical study
Data availability: GSE253781; Mendeley Data: https://doi.org/10.17632/jbx82vf585.1
Code availability: -