miR-338-3p and miR-34a-5p act as antagonists in phycocyanin-mediated process of ameliorating glycometabolism in T2DM HepG2 cells.

[Display omitted] • High level of miR-34a-5p and low level of miR-338-3p are expressed in T2DM cells. • miR-338-3p and miR-34a-5p act as antagonists in the phycocyanin-mediated process of T2DM amelioration. • PTPRM and NR3C2 are direct targets of miR-34a-5p and miR-338-3p, respectively. • miR-34a-5p/Ptprm and miR-338-3p/Nr3c2 axis are involved in phycocyanin-mediated glucose regulating process. Phycocyanin has been demonstrated to regulate glycometabolism. Previously, we discovered phycocyanin could protect against type 2 diabetes mellitus (T2DM), while its mechanism is still unclear. In this work, a miRNA-seq was employed to investigate potential vital miRNAs. The results indicated that miR-338-3p expression was decreased in T2DM, which was rescued by phycocyanin, while the expression of miR-34a-5p showed opposite trend. Knockdown miR-338-3p expression or overexpression of miR-34a-5p both reduced the glucose utilization of cells, while could be significantly reversed by phycocyanin. Dual-luciferase reporter assays suggested that PTPRM and NR3C2 are direct targets of miR-34a-5p and miR-338-3p, respectively. Strikingly, knockdown PTPRM expression impacted the uptake of glucose in normal cells, while interfering NR3C2 expression alleviated the decreased glucose availability caused by insulin resistance (IR). Thus, the present work demonstrated that miR-338-3p and miR-34a-5p act as antagonists in phycocyanin-mediated process of ameliorating glycometabolism, which highlights a critical role of miRNAs in regulating glycometabolism. [ABSTRACT FROM AUTHOR]