MiR-921 directly downregulates GPx3 in A549 lung cancer cells.

Glutathione peroxidase 3 (GPx3), a major antioxidant enzyme in plasma, catalyzes the reduction of HO, lipid peroxides and organic hydroperoxides by reducing glutathione (GSH). Hypermethylation of the GPx3 promoter and suppression of GPx3 expression are associated with inflammation, tumorigenesis, and response to chemotherapy in various types of cancer. We previously reported the possibility of GPx3 as a serological marker for lung cancer. In this study, we assessed the role of the microRNA (miRNA) hsa-miR-921 (miR-921) in the regulation of GPx3 expression in A549 lung cancer cells. The expression patterns of the miRNAs of A549, H1650, and H1975 cells were compared and analyzed. Of 25 miRNAs from the A549 cell line, the expression of 10 decreased and the expression of 15 increased in comparison to the miRNAs from the other cell lines. Of the miRNAs with reduced expression, the most reduced miRNA was miR-921 and the expected binding site of which is in the 3'-untranslated region (UTR) of GPx3. We found that miR-921 inhibited the expression of GPx3 and bound directly to the 3'-UTR of GPx3.