| Expression pattern: |
UP |
| Associated gene: |
NONO/p54nrb, LncNEAT1, METTL3, METTL14, KIAA1429 |
| Associated microRNA: |
- |
| Biological function: |
Facilitates intracellular lipid accumulation, tumor cell growth/proliferation, and adaptive survival under lipid overload; reduces apoptosis; promotes malignant progression of MASH-related HCC. |
| Molecular mechanism: |
m6A-dependent interaction with NONO/p54nrb to assemble intranuclear paraspeckles and promote nuclear retention; recruitment to DSB foci to form RNA-DNA hybrids (R loops), driving chromatin remodeling with increased TAD contact/fusion and selective gene activation. |
| Biological pathway or process: |
proliferation (promotes); apoptosis (inhibits); lipid metabolism (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; ISH (In Situ Hybridization); FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNase R Treatment; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; MeRIP / MeRIP-seq; RIP (RNA Immunoprecipitation); RNA Pull-Down; CLIP; Luciferase Reporter Assay; Transfection; TUNEL; IF (Immunofluorescence); Western Blot; In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
circTACC3 is specifically upregulated and highly m6A-modified in MASH-related HCC tumors but not in HBV-HCC, and its expression level and m6A modification status are suggested as a promising diagnostic marker and therapeutic target for MASH-related HCC. |
| Description: |
circTACC3 is up-regulated and nuclear-enriched in MASH-related HCC. In lipid overload, its m6A-dependent binding to NONO/p54nrb promotes paraspeckle assembly and nuclear retention, enabling recruitment to DSB sites to form circTACC3-containing R loops that remodel chromatin (enhanced inter-TAD contacts/fusion) and activate malignant programs, promoting proliferation, lipid accumulation, and survival. |
| Confidence score: |
0.8227 |