circRNA basic information
circBase ID: hsa_circ_0000745
Name: hsa_circ_SPECC1
Synonym: circSPECC1 / circ_0000745
Host Gene: SPECC1
Genomic location(hg19): chr17:20107645-20109225:+
Genomic location(hg38): chr17:20204332-20205912:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0018177
MONDO name: glioblastoma
Disease details: glioblastoma / GBM
Disease DO ID:
 3068
Disease MeSH ID:
 D005909
Disease NCIt ID:
 C3058
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

primary human glioblastoma (GBM) tissue specimens; recurrent human GBM tissue specimens
Cell lines:

LN229; U251; LN229R; U251R; 293 T; A172; U87; SNB19; T98G; UC2
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: IGF2BP1, ANXA2, EGFR, AKT, SPECC1-415aa
Associated microRNA: -
Biological function: Suppresses proliferation, migration, invasion, and colony formation of GBM cells; restores TMZ sensitivity in TMZ-resistant GBM cells; affects DNA damage repair capacity under TMZ.
Molecular mechanism: circSPECC1 encodes SPECC1-415aa; IGF2BP1 (m6A reader) binds circSPECC1 to promote its stability; SPECC1-415aa binds ANXA2 and competitively inhibits ANXA2-EGFR binding, reducing EGFR (Tyr845) and AKT (Ser473) phosphorylation, restoring TMZ sensitivity.
Biological pathway or process:

proliferation (inhibits); migration (inhibits); invasion (inhibits); PI3K/AKT (inhibits); EGFR (inhibits); apoptosis (promotes); other pathway/process (promotes)
Detected method:
Q
M
Validation methods:

Microarray; RT-qPCR; Clinical Sample Validation; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Transfection; CCK8; Wound Healing Assay; Transwell Assay; Colony Formation Assay; IF (Immunofluorescence); MeRIP / MeRIP-seq; RIP (RNA Immunoprecipitation); RNA-seq; Bioinformatics Analysis; Western Blot; Luciferase Reporter Assay; RNA Pull-Down; Co-IP; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; TUNEL
Clinical significance:

circSPECC1 is lower in recurrent GBM than primary GBM and is associated with TMZ sensitivity/resistance; proposed as a potential molecular target to improve TMZ resistance and prevent recurrence.
Description:

circSPECC1 (hsa_circ_0000745), derived from SPECC1, is down-regulated in recurrent GBM and TMZ-resistant GBM cells. It suppresses malignant phenotypes and restores TMZ sensitivity mainly by encoding the peptide SPECC1-415aa, which binds ANXA2 and blocks ANXA2-EGFR interaction, thereby inhibiting EGFR/AKT signaling; IGF2BP1 binding (m6A-dependent) promotes circSPECC1 stability.
Confidence score:

0.8886
Other information
Title:

A novel protein SPECC1-415aa encoded by N6-methyladenosine modified circSPECC1 regulates the sensitivity of glioblastoma to TMZ.

Journal: Cellular & molecular biology letters
Published: 2024
PubMed ID: 39333871
Study type:

combined biological and clinical study
Data availability: -
Code availability: -