circRNA basic information
circBase ID: hsa_circ_0000745
Name: hsa_circ_SPECC1
Synonym: circSPECC1
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:
 0001056
MONDO name: gastric cancer
Disease details: gastric cancer
Disease DO ID:
 10534
Disease MeSH ID:
 -
Disease NCIt ID:
 C9331
Disease ICD11 ID:
 1397617262
Disease OMIM ID:
 613659
Species: Human
Species details: Homo sapiens
Tissue specimen:

gastric cancer tissues; corresponding adjacent tissues; primary lesions; metastatic lesions; lung metastatic tissues
Cell lines:

AGS; MKN28; MGC803; MKN74; HGC27; BGC823; HEK293; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: ATG4B, RNF5, ELAVL1/HuR
Associated microRNA: -
Biological function: CircSPECC1 suppresses ATG4B-mediated autophagy, enhances anoikis, inhibits anoikis resistance, and reduces gastric cancer metastasis.
Molecular mechanism: CircSPECC1 physically interacts with ATG4B and RNF5 to form a trimer complex, promotes ATG4B liquid-liquid phase separation and ubiquitination/degradation, thereby suppressing autophagy and enhancing anoikis. m6A-dependent ELAVL1/HuR recognition suppresses circSPECC1, increasing ATG4B and anoikis resistance; lopinavir blocks ELAVL1-circSPECC1 interaction and restores circSPECC1.
Biological pathway or process:

autophagy (inhibits); apoptosis (promotes); metastasis (inhibits); ubiquitination (promotes); m6A modification (other); other pathway/process (promotes)
Detected method:
Q
H
Validation methods:

RT-qPCR; ISH (In Situ Hybridization); FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; MeRIP / MeRIP-seq; Transfection; Annexin V/PI Flow Cytometry; CCK8; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; H&E Staining; Survival Analysis; ROC Analysis; Bioinformatics Analysis; Cohort Study
Clinical significance:

CircSPECC1 is decreased in gastric cancer tissues, negatively correlated with TNM stage, lymphatic metastasis, distant metastasis and ATG4B expression; low circSPECC1 expression is associated with poor survival, and conjoint analysis with ATG4B can predict prognosis.
Description:

CircSPECC1 is downregulated in gastric cancer and acts as an anti-metastatic circRNA by binding ATG4B and RNF5, promoting ATG4B phase separation, ubiquitination and degradation. Its loss increases ATG4B-mediated autophagy and anoikis resistance, while lopinavir restores circSPECC1 by blocking ELAVL1/HuR-mediated repression, thereby enhancing anoikis and reducing metastasis. Low circSPECC1 expression is associated with advanced disease features and poor survival.
Confidence score:

0.837
Other information
Title:

Lopinavir enhances anoikis by remodeling autophagy in a circRNA-dependent manner.

Journal: Autophagy
Published: 2024
PubMed ID: 38433354
Study type:

combined biological and clinical study
Data availability: All data supporting this paper are presented within the paper and/or the Supplementary Materials; datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request
Code availability: -