Additionally, the increased levels of PTEN correlates with longer survival.50 Mechanically, PTEN activates PIP3 to PIP2, and then inhibits PI3K/AKT signaling pathway which meditates embryonic development, cell viability, apoptosis, differentiation, migration, and metastasis.51, 52, 53 The present data indeed proved that celastrol induced PTEN upregulation and significantly inhibited PI3K/AKT signaling pathway in CCA cells. The gene discussed is PTEN; the disease is cholangiocarcinoma.