circRNA basic information
circBase ID: hsa_circ_0077495
Name: hsa_circ_ASCC3
Synonym: circASCC3
Host Gene: ASCC3
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
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; matched normal tissues; matched peritumor tissues; tumor tissues; biopsied tissues; plasma
Cell lines:

A549; H1299; H460; H1703; LLC/LUC; HEK-293T; THP-1
In vivo animal model:

cell line-derived xenograft; syngeneic model
circRNA-disease information
Expression pattern:
UP
Associated gene: C5, C5a, C5aR, CD8 + T cells, macrophages, PD-L1, IL-6, JAK2/STAT3 pathway
Associated microRNA: miR-432-5p
Biological function: circASCC3 promotes NSCLC cell proliferation, migration, invasion, lung metastasis, EMT, macrophage M2-like polarization, PD-L1 upregulation, CD8 + T-cell dysfunction, immunosuppressive tumor microenvironment, and anti-PD1 resistance.
Molecular mechanism: circASCC3 acts as a miR-432-5p sponge to upregulate C5/C5a, activates the C5a/C5aR axis, induces EMT, promotes macrophage immunosuppressive polarization and PD-L1 expression, and contributes to CD8 + T-cell exhaustion and anti-PD1 resistance.
Biological pathway or process:

ceRNA regulation (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); EMT (promotes); macrophage polarization (promotes); immune regulation (inhibits); JAK/STAT (promotes); drug resistance (promotes)
Detected method:
Q
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; RT-qPCR; FISH / smFISH; Clinical Sample Validation; circRIP; RNA Pull-Down; Luciferase Reporter Assay; RNA-seq; Transfection; CCK8; Colony Formation Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; Flow Cytometry（Non-apoptosis/cycle）; Annexin V/PI Flow Cytometry; ELISA; Western Blot; IHC (Immunohistochemistry); IF (Immunofluorescence); H&E Staining; Cohort Study; Survival Analysis; Bioinformatics Analysis
Clinical significance:

High circASCC3 expression is associated with larger tumor size, lymph node metastasis, advanced TNM stage, higher postoperative recurrence rate, shorter OS, poor RFS and OS, and reduced efficacy of anti-PD1 therapy; circASCC3 may be a biomarker to predict anti-PD1 efficacy.
Description:

circASCC3 is up-regulated in NSCLC and further elevated in anti-PD1-refractory patients. It promotes NSCLC progression and anti-tumor immune suppression by sponging miR-432-5p to increase C5/C5a, thereby inducing EMT, M2-like macrophage polarization, PD-L1 upregulation, CD8 + T-cell dysfunction, and resistance to PD1 blockade. High circASCC3 expression is associated with poor prognosis and reduced anti-PD1 efficacy.
Confidence score:

0.8961
Other information
Title:

Elevated circASCC3 limits antitumor immunity by sponging miR-432-5p to upregulate C5a in non-small cell lung cancer.

Journal: Cancer letters
Published: 2022
PubMed ID: 35667514
Study type:

combined biological and clinical study
Data availability: All the data in our study are available upon request; Supplementary data to this article can be found online at https://doi. org/10.1016/j.canlet.2022.215774.
Code availability: -