Abstract
Arsenic (As) is a natural hepatotoxicity inducer that is found ubiquitously in foods and environmental media. We found that arsenite exposure elicits autophagy in vivo and vitro, the specific role and regulatory mechanism of which are yet clear. MicroRNAs (miRNAs) are short noncoding RNAs that function in the posttranscriptional regulation of gene expression. Here, we report that miR-122, the most enriched constitutive miRNA in the liver, induced cell protective autophagy in arsenite-exposed hepatocytes. Arsenite exposure elevated miRNA-122 level and decreased the level of its target gene, PKM2. Under arsenic stress, overexpression of miR-122 significantly induced cell protective autophagy, characterized by lipidation of LC3-II and a corresponding consumption of p62. Conversely, autophagy inhibition by miR-122 knockdown was reversed by si-PKM2 cotransfection. We also found that miR-122 knockdown positively regulated the PI3K/Akt/mTOR pathway, and this phenomenon was reversed by cotransfecting cells with si-PKM2. Taken together, our findings show that the miR-122/PKM2 autophagy axis protects hepatocytes from arsenite stress via the PI3K/Akt/mTOR pathway; thus, miR-122 may be a potential candidate in the treatment of arseniasis.