circRNA basic information
circBase ID: -
Name: hsa_circ_TBC1D14
Synonym: circTBC1D14 / hsa_circRNA_103598
Host Gene: TBC1D14
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: nucleus
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple-negative breast cancer / TNBC
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:

TNBC tumor tissue; adjacent normal breast tissue; breast cancer tissue; xenograft tumor tissue; lung tissue

Cell lines:

MDA‐MB‐231(MDA231); MDA‐MB‐468(MDA468); MCF‐7; T47D; SKBR‐3; MCF‐10A; HEK‐293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: FUS, PRMT1, LAMP1, VHL mRNA, eIF2alpha, HIF-1alpha, G3BP1, FMRP, P62, LC3B, Atg-5, Atg7, Atg12, Ran
Associated microRNA: -
Biological function: Promotes TNBC progression by enhancing proliferation, migration/invasion, stress granule dynamics, and lysosome-associated autophagy flux under hypoxic conditions; stabilizes PRMT1 and increases HIF-1alpha via inhibiting VHL translation.
Molecular mechanism: circTBC1D14 interacts with FUS to promote circRNA biogenesis and forms hypoxia-induced FUS-circTBC1D14 stress granules; circTBC1D14 binds PRMT1 and inhibits K48-linked polyubiquitination to stabilize PRMT1; recruits LAMP1 and reinforces FUS-LAMP1 interaction to enhance lysosome-associated autophagy flux; co-localizes VHL mRNA in SGs to inhibit VHL translation, increasing HIF-1alpha.
Biological pathway or process:

autophagy (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); ubiquitination (inhibits); HIF-1 signaling (promotes); mitochondrial function (other); other pathway/process (other)

Detected method:
Q
Validation methods:

RT-qPCR; RNase R Treatment; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Western Blot; Co-IP; Luciferase Reporter Assay; Transfection; MTT; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis; circRNA-seq

Clinical significance:

High circTBC1D14 expression is associated with poor prognosis and predicts poor overall survival in breast cancer/TNBC; circTBC1D14 could be considered as an independent prognostic factor for overall survival of patients.

Description:

circTBC1D14 is up-regulated in TNBC and promotes tumor growth and metastasis, particularly under hypoxia. Mechanistically, it forms hypoxia-induced stress granules with FUS and promotes lysosome-associated autophagy by recruiting LAMP1, while stabilizing PRMT1 via inhibition of K48-linked polyubiquitination and enhancing hypoxia signaling through the VHL/HIF-1alpha axis.

Confidence score:

0.8856

Other information
Title:

Hypoxia-Induced FUS-circTBC1D14 Stress Granules Promote Autophagy in TNBC.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published: 2023
PubMed ID: 36806670
Study type:

combined biological and clinical study

Data availability: GSE101124
Code availability: -