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.
Dai
Rongyang
R
Department of Biochemistry of Luzhou Medical College, Luzhou 646000, Sichuan, China.
Li
Juan
J
Liu
Youping
Y
Yan
Dongmei
D
Chen
Shaokun
S
Duan
Chunyan
C
Liu
Xiaoyan
X
He
Tao
T
Li
Hong
H
D017209:Apoptosis; D002453:Cell Cycle; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D014407:Tumor Cells, Cultured
D050760:Cyclin-Dependent Kinase Inhibitor p27; D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D020929:Mitogen-Activated Protein Kinase Kinases; C436291:CDKN1B protein, human; C525709:MIR221, human; C525710:MIR222, human