hCINAP is potentially a direct target gene of HIF-1 and is required for hypoxia-induced EMT and apoptosis in cervical cancer cells.

The early metastasis of cervical cancer is a multistep process requiring the cancer cells to adapt to the signal input from different tissue environments, including hypoxia. Hypoxia-induced epithelial-to-mesenchymal transition (EMT) plays a critical role in the ability to invade surrounding tissues. However, the molecular mechanisms underlying EMT in cervical cancer remain to be elucidated. Herein, we show that hypoxia-inducible factor-1alpha (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT) are recruited to the human coilin-interacting nuclear ATPase protein (hCINAP) promoter and initiate hCINAP expression in hypoxia. Ablation of hCINAP decreased the migratory capacity and EMT of cervical cancer cells under hypoxic conditions. Furthermore, hCINAP regulated EMT through the Akt-mTOR signaling pathway, and inhibits hypoxia-induced p53-dependent apoptosis. Our data collectively show that hCINAP may have essential roles in the metastasis of cervical cancer and could be a potential target for curing cervical cancer.