Since the expression of mir-196a-3p was significantly upregulated in tumorspheres compared to adherent tumor cells (Fig. 3C), and the expression level of DHFR was significantly decreased in inner cells compared to that in outer cells of tumorspheres (Fig. 3A), we speculate that the HIF-miR-196a-3p-DHFR axis may play an important role in altering the pattern of one-carbon metabolism in tumorsphere cells under hypoxia conditions. This evidence concerns the gene DHFR and neoplasm.