circRNA basic information
circBase ID: hsa_circ_0009910
Name: hsa_circ_MFN2
Synonym: circMFN2
Host Gene: MFN2
Genomic location(hg19): chr1:12049221-12052747:+
Genomic location(hg38): chr1:11989164-11992690:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma
Disease DO ID:
684, 686
Disease MeSH ID:
D006528
Disease NCIt ID:
C3099
Disease ICD11 ID:
1294035808
Disease OMIM ID:
114550
Species: Human
Species details: Homo sapiens
Tissue specimen:

HCC tissue specimens; HCC tissues; adjacent non-tumor tissues; normal liver tissues; tumor tissues; para-cancerous tissues; lung tissues

Cell lines:

Hep-G2; Focus; Hep-3B; MHCC-97L; HCC-LM3; YY8103; Huh-7; THLE-2; 293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: AGO2, ELK1, MFN2, phosphorylated ELK1, SLC1A5
Associated microRNA: miR-361-3p
Biological function: Promotes HCC cell proliferation, migration, invasion, tumor growth, metastasis, and glutaminolysis; high circMFN2 expression is associated with worse prognosis.
Molecular mechanism: circMFN2 functions as a cytoplasmic ceRNA sponge for miR-361-3p, upregulates ELK1, and participates in a circMFN2/miR-361-3p/ELK1 positive feedback loop in which ELK1 promotes MFN2 transcription and indirectly increases circMFN2; circMFN2 promotes glutaminolysis through increased ELK1 phosphorylation at Ser383.
Biological pathway or process:

ceRNA regulation (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); glutaminolysis (promotes); ferroptosis (inhibits)

Detected method:
Q
H
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Microarray; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); IF (Immunofluorescence); Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

High circMFN2 expression was associated with TNM stage, microvascular invasion, differentiation, tumor size, metastasis, shorter overall survival and disease-free survival, and was an independent prognostic factor for poor survival and recurrence; circMFN2 could be a potential biomarker of HCC diagnosis and prognosis and a therapeutic target.

Description:

circMFN2/hsa_circ_0009910 is an upregulated circRNA derived from MFN2 in HCC. It acts as an oncogenic cytoplasmic ceRNA by sponging miR-361-3p, thereby increasing ELK1 and forming a positive circMFN2/miR-361-3p/ELK1 feedback loop that promotes proliferation, migration, invasion, metastasis, and glutaminolysis through phosphorylated ELK1. Clinically, high circMFN2 expression predicts poor OS and DFS and may serve as a prognostic biomarker and therapeutic target.

Confidence score:

0.9019

Other information
Title:

CircMFN2/miR-361-3p/ELK1 feedback loop promotes glutaminolysis and the progression of hepatocellular carcinoma.

Journal: Cancer letters
Published: 2025
PubMed ID: 39933635
Study type:

combined biological and clinical study

Data availability: GSE78520; GSE94508; GSE155949; Supplementary Table S1; Supplementary Table S2; Supplementary Table S3; Supplementary Table S4; Supplementary Table S5; Supplementary Tables S6 and S7; supplementary information files; https://doi.org/10.1016/j.canlet.2025.217473
Code availability: -