circRNA basic information
circBase ID: hsa_circ_0001546
Name: hsa_circ_FAM114A2
Synonym: circ_0001546
Host Gene: FAM114A2
Genomic location(hg19): chr5:153413350-153414527:-
Genomic location(hg38): chr5:154033790-154034967:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005140
MONDO name: ovarian carcinoma
Disease details: epithelial ovarian cancer / EOC
Disease DO ID:
4001
Disease MeSH ID:
-
Disease NCIt ID:
C4908
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

normal ovarian tissues; EOC tissues; primary ovarian cancer tissue; omentum metastasis tissues; peritoneum metastasis tissues; xenograft tumors

Cell lines:

HOSEpiC; OVCAR8; TOV-112D; A2780; HO8910; HEY; SKOV3; HEK293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: 14-3-3 proteins, YWHAB, YWHAH, YWHAQ, YWHAZ, CAMK2D, Tau, p-Tau (S324), p-Tau (S214), GPX4
Associated microRNA: -
Biological function: Inhibits EOC proliferation, migration, and peritoneal metastasis; promotes Tau aggregation-dependent LPO accumulation and ferroptosis.
Molecular mechanism: Acts as a chaperone molecule by directly binding 14-3-3 proteins, stabilizing them and facilitating recruitment of CAMK2D to phosphorylate Tau at Ser324, forming a hsa_circ_0001546/14-3-3/CAMK2D/Tau complex that drives Tau aggregation, LPO accumulation, and ferroptosis.
Biological pathway or process:

ferroptosis (promotes); lipid metabolism (promotes); metastasis (inhibits); migration (inhibits); invasion (inhibits); proliferation (inhibits); other pathway/process (promotes)

Detected method:
Q
H
S
Validation methods:

RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; RNA Pull-Down; RIP (RNA Immunoprecipitation); Western Blot; Co-IP; IF (Immunofluorescence); In Vivo Animal Model; ISH (In Situ Hybridization); IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis

Clinical significance:

High hsa_circ_0001546 levels were associated with better overall survival and better disease-free survival in the FUSCC cohort.

Description:

hsa_circ_0001546 is down-regulated in epithelial ovarian cancer and functions as a tumor suppressor. It binds 14-3-3 proteins as a chaperone/scaffold to recruit CAMK2D, promoting Tau Ser324 phosphorylation and Tau aggregation, which increases lipid peroxides and induces LPO-dependent ferroptosis, thereby inhibiting EOC peritoneal metastasis. High hsa_circ_0001546 expression is associated with better OS and DFS.

Confidence score:

0.8826

Other information
Title:

Tau Aggregation-Dependent Lipid Peroxide Accumulation Driven by the hsa_circ_0001546/14-3-3/CAMK2D/Tau Complex Inhibits Epithelial Ovarian Cancer Peritoneal Metastasis.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published: 2024
PubMed ID: 38634567
Study type:

combined biological and clinical study

Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Code availability: -