circRNA basic information
circBase ID: hsa_circ_0004291
Name: hsa_circ_POLA2
Synonym: circPOLA2
Host Gene: POLA2
Genomic location(hg19): chr11:65061623-65063461:+
Genomic location(hg38): chr11:65294152-65295990:+
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; adjacent normal tissues; xenograft tumors

Cell lines:

A549; PC9; H1975; H1299; BBM; HEK-293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: Merlin
Associated microRNA: -
Biological function: sensitizes NSCLC cells to ferroptosis; promotes lipid peroxidation; suppresses proliferation, migration, invasion and tumor growth
Molecular mechanism: circPOLA2 binds Merlin and restricts Merlin phosphorylation at S518, activating Hippo signaling and inhibiting YAP to increase ferroptosis sensitivity and suppress tumorigenesis
Biological pathway or process:

Hippo/YAP (inhibits); ferroptosis (promotes); proliferation (inhibits); migration (inhibits); invasion (inhibits)

Detected method:
Q
S
Validation methods:

circRNA-seq; Bioinformatics Analysis; RT-qPCR; Clinical Sample Validation; ROC Analysis; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RNA Pull-Down; RIP (RNA Immunoprecipitation); Transfection; Western Blot; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Flow Cytometry(Non-apoptosis/cycle); In Vivo Animal Model; IHC (Immunohistochemistry)

Clinical significance:

downregulated in NSCLC and correlated with advanced clinical stage; diagnostic value with AUC 0.879

Description:

circPOLA2 (hsa_circ_0004291) is down-regulated in NSCLC and acts as a tumor suppressor by promoting lipid peroxidation/ferroptosis and inhibiting proliferation and metastasis-related behaviors. Mechanistically, it binds Merlin, reduces Merlin Ser518 phosphorylation, activates Hippo signaling and suppresses YAP activity, increasing ferroptosis sensitivity and inhibiting tumor growth.

Confidence score:

0.8832

Other information
Title:

CircPOLA2 sensitizes non-small cell lung cancer cells to ferroptosis and suppresses tumorigenesis via the Merlin-YAP signaling pathway.

Journal: iScience
Published: 2024
PubMed ID: 39310771
Study type:

combined biological and clinical study

Data availability: GEO: GSE254362; GSE101684; GSE112214
Code availability: -