Laboratory study uncovers that m6A-modified circFADS2 drives hepatocellular carcinoma progression via CAPRIN1 and TYMS, highlighting a potential therapeutic target.
Key Points
To determine the biological role, clinical relevance, and downstream molecular mechanism of circFADS2 in hepatocellular carcinoma.
Screened candidate circRNAs across three Gene Expression Omnibus datasets (GSE155949, GSE235991, and GSE263134) and validated circFADS2 expression and circular structure via RT-qPCR, RNase R digestion, and Sanger sequencing.
Evaluated HCC cell proliferation, invasion, and apoptosis using EdU incorporation, Transwell assays, and flow cytometry following circFADS2 knockdown.
Characterized molecular interactions and m6A regulation using MeRIP-qPCR, RNA pull-down, RNA immunoprecipitation, actinomycin D decay assays, and Western blotting.
circFADS2 was significantly elevated in HCC tissues and cell lines, correlating positively with larger tumor size, microvascular invasion, and advanced TNM stage.
circFADS2 silencing suppressed HCC cell proliferation and invasion while inducing apoptosis, counteracting the oncogenic effects of METTL3 overexpression.
METTL3 catalyzed the m6A modification that upregulated circFADS2, which directly bound CAPRIN1 to stabilize TYMS mRNA and sustain malignant phenotypes.