miR-221/222 suppression protects against endoplasmic reticulum stress-induced apoptosis via p27(Kip1)- and MEK/ERK-mediated cell cycle regulation.

Cancer cells are relatively resistant to endoplasmic reticulum (ER) stress-induced apoptosis. However, the underlying mechanisms remain largely unclear. We observed that the microRNAs miR-221/222 are associated with apoptosis regulation under ER stress in human hepatocellular carcinoma (HCC) cells. Induction of ER stress does not trigger significant apoptosis but obviously causes downregulation of miR-221/222 in HCC cells. In these cells, ER stress-induced apoptosis is enhanced by miR-221/222 mimics and attenuated by miR-221/222 inhibitors. miR-221/222 promoted-apoptosis under ER stress is associated with p27(Kip1)- and MEK/ERK-mediated cell cycle regulation. Our results suggest that suppression of miR-221/222 plays a crucial role in the protection against apoptosis induced by ER stress in HCC cells.