MicroRNA-424 Predicts a Role for {beta}-1,4 Branched Glycosylation in Cell Cycle Progression [Cell Biology]

November 20th, 2015 by Vaiana, C. A., Kurcon, T., Mahal, L. K.

MicroRNA (miRNA) regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. The human microRNA hsa-miR-424 is upregulated in response to anti-proliferative cytokines, and directly represses cell cycle progression. Our lab recently established that miRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). Herein, we identify MGAT4A, OGT and GALNT13 as targets of miR-424. MGAT4A, but not the other two glycogenes, is regulated by miR-424 in the mammary epithelial cancer cell line MCF-7. Knockdown of MGAT4A in MCF-7 induces cell cycle arrest through decreasing CCND1 and CDC25A levels. Loss of MGAT4A does not affect levels of β-(1,6) branched N-glycans, arguing that this effect is not due to gross changes in N-glycan branching but rather is specific to the β-(1,4) branch. This is the first example of miR-424 regulation of glycosylation related genes, lending insight into one possible mechanism by which cells use specific branched glycosylation patterns to regulate cell cycle progression.