| Expression pattern: |
UP |
| Associated gene: |
VEGFA, VEGFR, HIF-1alpha, CXCR4, Hbp-1, PMN-MDSCs, exosomes |
| Associated microRNA: |
miR-29a-3p, miR-29b-3p, miR-29b-3c |
| Biological function: |
promotes proliferation, migration and invasion of HCC cells; promotes lymph node metastasis; promotes exosome secretion and exosomal miR-29a-3p enrichment; induces an immunosuppressive LN microenvironment via PMN-MDSCs |
| Molecular mechanism: |
ceRNA sponge of miR-29a-3p to regulate VEGFA and downstream PI3K-Akt-mTOR/HIF-1alpha/CXCR4; circ-0044539-HIF-1alpha axis increases exosome secretion and exosomal miR-29a-3p transfer to PMN-MDSCs to suppress Hbp-1 |
| Biological pathway or process: |
PI3K/AKT/mTOR (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); immune regulation (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; Bioinformatics Analysis; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; Western Blot; IHC (Immunohistochemistry); In Vivo Animal Model; H&E Staining; Clinical Sample Validation |
| Clinical significance: |
serum circ-0044539 was higher in HCC patients with LNM and may serve as a potential biomarker for the diagnosis of HCC LNM |
| Description: |
circ-0044539 (hsa_circ_0044539, host gene COL1A1) is up-regulated in HCC with lymph node metastasis and promotes HCC proliferation, migration, invasion and LNM. Mechanistically, it sponges miR-29a-3p to increase VEGFA and activate the PI3K-AKT-mTOR/HIF-1alpha/CXCR4 cascade, and via a HIF-1alpha-dependent mechanism increases exosome secretion and exosomal miR-29a-3p transfer to PMN-MDSCs to suppress Hbp-1 and enhance immunosuppression in lymph nodes. Serum circ-0044539 is elevated in LNM cases, supporting its biomarker potential. |
| Confidence score: |
0.843 |