circRNA basic information
circBase ID: hsa_circ_0004623
Name: hsa_circ_HIF1A
Synonym: circHIF1A
Host Gene: HIF1A
Genomic location(hg19): chr14:62187099-62194373:+
Genomic location(hg38): chr14:61720381-61727655:+
Subcellular localization: cytoplasm; exosome; extracellular
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple-negative breast cancer
Disease DO ID:
0060081
Disease MeSH ID:
D064726
Disease NCIt ID:
C71732
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

breast cancer tissues; paired adjacent normal tissues; adjacent normal breast cells; plasma; xenograft tumors; lungs

Cell lines:

MDA-MB-231; MDA-MB-468; HEK293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: NFIB, FUS, AGO2, HIF1A, P21, AKT/STAT3 signaling pathway
Associated microRNA: miR-149-5p
Biological function: Promotes TNBC cell proliferation, growth, DNA synthesis, migration and metastasis; inhibits apoptosis; enhances breast cancer progression via exosomal communication.
Molecular mechanism: circHIF1A functions as a miRNA sponge for miR-149-5p to upregulate NFIB, directly binds NFIB protein to promote NFIB nuclear translocation, activates AKT/STAT3 signaling and inhibits P21; FUS promotes circHIF1A biogenesis and NFIB transcriptionally activates FUS, forming a circHIF1A/NFIB/FUS positive feedback loop; circHIF1A can also be packaged into exosomes.
Biological pathway or process:

proliferation (promotes); migration (promotes); metastasis (promotes); apoptosis (inhibits); cell cycle (promotes); PI3K/AKT (promotes); JAK/STAT (promotes); ceRNA regulation (promotes); other pathway/process (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; ISH (In Situ Hybridization); FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; MTT; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; Western Blot; IHC (Immunohistochemistry); Cohort Study; Survival Analysis; ROC Analysis; Bioinformatics Analysis

Clinical significance:

High circHIF1A expression is associated with metastasis, TNBC subtype and poor prognosis; circulating plasma circHIF1A distinguishes breast cancer patients from healthy controls and may serve as a diagnostic biomarker and therapeutic target.

Description:

circHIF1A is a HIF1A-derived human circRNA upregulated in breast cancer and TNBC, where high expression is associated with lymph node metastasis, TNBC subtype and poor overall survival. It promotes TNBC proliferation, migration, metastasis and tumor growth by sponging miR-149-5p, increasing NFIB expression and nuclear translocation, activating AKT/STAT3 signaling and repressing P21, while FUS and NFIB form a positive feedback loop that enhances circHIF1A biogenesis. circHIF1A is also secreted in exosomes and elevated in patient plasma, supporting its potential as a diagnostic biomarker and therapeutic target.

Confidence score:

0.9043

Other information
Title:

CircHIF1A regulated by FUS accelerates triple-negative breast cancer progression by modulating NFIB expression and translocation.

Journal: Oncogene
Published: 2021
PubMed ID: 33714984
Study type:

combined biological and clinical study

Data availability: TCGA; GSE40267; Supplementary Information available at https://doi.org/10.1038/s41388- 021-01739-z
Code availability: -