Effects of OLFM2B knockout on malignant phenotypes and underlying mechanisms in Hepatocellular Carcinoma

Here, we report that knockdown of OLFML2B significantly suppresses the malignant phenotype of HCC cells in vitro and in vivo. Specifically, OLFML2B depletion inhibited cell proliferation, migration, invasion, and epithelial‑mesenchymal transition (EMT), while promoting apoptosis and impairing angiogenesis.

Mechanistically, transcriptomic and bioinformatic analyses linked high OLFML2B expression to activation of the PI3K/AKT pathway and key oncogenic signatures including proliferation, EMT, and hypoxia. These findings were corroborated by Western blot and qPCR, showing downregulation of PI3K/AKT signaling and EMT markers upon OLFML2B knockdown. Notably, OLFML2B‑silenced HCC cells exhibited enhanced sensitivity to sorafenib, regorafenib, and cabozantinib.