Conclusion
Our findings demonstrate that hnRNPA1 promotes HCC progression by regulating ZNF207 splicing and the PI3K/Akt/mTOR pathway. hnRNPA1-ZNF207 interaction represents a potential therapeutic target for HCC, providing insights into the molecular mechanisms underlying HCC progression.
Methods
We analyzed hnRNPA1 expression in HCC tissues compared to non-tumor tissues using RNA-seq and immunohistochemistry. hnRNPA1 was knocked down in Hep G2 cells to assess its impact on cell proliferation, migration, and apoptosis using scratch assays, flow cytometry, qPCR, and Western blot. We also explored the interaction between hnRNPA1 and ZNF207, as well as its splicing effects and downstream signaling pathways by RIP assay, bioinformatics, qPCR and Western blot.
Results
hnRNPA1 was significantly upregulated in HCC tissues compared to normal tissues, correlating with poor patient survival. hnRNPA1 knockdown reduced Hep G2 cell proliferation and migration while increasing apoptosis. We identified that hnRNPA1 bound to ZNF207 and regulated its exon 9 skipping, influencing ZNF207 splicing and the PI3K/Akt/mTOR pathway, key regulators of cell growth and survival.