circRNA basic information
circBase ID: -
Name: hsa_circ_RACGAP1
Synonym: circ_rac GTPaseeactivating protein 1 / hsa_circ_101053
Host Gene: RACGAP1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005233
MONDO name: non-small cell lung carcinoma
Disease details: non-small cell lung cancer / NSCLC
Disease DO ID:
3908
Disease MeSH ID:
D002289
Disease NCIt ID:
C2926
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

NSCLC tissues; adjacent normal lung tissues; serum samples; serum-derived exosomes; tumor tissues; lung tissues

Cell lines:

A549; H1299; H1975; H460; PC-9; 16HBE

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: polypyrimidine tractebinding protein 1 / PTBP1, sirtuin-3 / SIRT3, replication timing regulatory factor 1 / RIF1
Associated microRNA: -
Biological function: Facilitates NSCLC cell stemness, migration, invasion, EMT, tumor growth, and metastasis; circRACGAP1 depletion represses these malignant phenotypes.
Molecular mechanism: circRACGAP1 recruits the RNA-binding protein PTBP1 to enhance SIRT3 mRNA stability and expression, promoting SIRT3-mediated RIF1 deacetylation and activation of the Wnt/b-catenin pathway.
Biological pathway or process:

Wnt/beta-catenin (promotes); stemness (promotes); metastasis (promotes); EMT (promotes); migration (promotes); invasion (promotes); proliferation (promotes); mRNA stability (promotes); other pathway/process (promotes)

Detected method:
Q
Validation methods:

RNase R Treatment; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Actinomycin D / DRB Stability Assay; Transfection; Flow Cytometry(Non-apoptosis/cycle); Wound Healing Assay; Transwell Assay; Western Blot; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Survival Analysis; Bioinformatics Analysis

Clinical significance:

Exosomal circRACGAP1 is upregulated in patients with NSCLC and high expression is associated with lower overall survival, suggesting biomarker potential.

Description:

circRACGAP1 is upregulated in NSCLC tissues, cell lines, and serum-derived exosomes, and high exosomal circRACGAP1 is associated with poor overall survival. Functionally, circRACGAP1 promotes NSCLC stemness, EMT, migration, invasion, tumor growth, and metastasis. Mechanistically, it recruits PTBP1 to stabilize SIRT3, leading to RIF1 deacetylation and activation of the Wnt/beta-catenin pathway.

Confidence score:

0.8768

Other information
Title:

circ_rac GTPase-Activating Protein 1 Facilitates Stemness and Metastasis of Non-Small Cell Lung Cancer via Polypyrimidine Tract-Binding Protein 1 Recruitment to Promote Sirtuin-3-Mediated Replication Timing Regulatory Factor 1 Deacetylation.

Journal: Laboratory investigation; a journal of technical methods and pathology
Published: 2023
PubMed ID: 36748197
Study type:

combined biological and clinical study

Data availability: The data sets used or analyzed in the current study are available from the corresponding author upon reasonable request.
Code availability: -