Dysregulated miRNAs contribute to altered placental glucose metabolism in patients with gestational diabetes via targeting GLUT1 and HK2

Aberrantly Expressed Non-Coding RNAs in the Placenta and Their Role in the Pathophysiology of Gestational Diabetes Mellitus

“…In vitro experiments indicated that miR-9 and miR-22 inhibitors increased glucose uptake and lactate secretion in primary syncytiotrophoblasts (STBs) and HTR8/SVneo cells by targeting GLUT1 and HK2. 30 Another study revealed that downregulation of miR-30d-5p promoted glucose uptake of HTR8 cells, which could be attenuated by downregulation of RAB8A. However, there were no differences between the miR-30d-5p mimic and pre-miR control on cell glucose uptake of HTR8 cells.…”

“…A recent study demonstrated that miR-9 and miR-22 play a role in disordered glucose metabolism in the placentas of patients with GDM by targeting GLUT1 and hexokinase-2 (HK2). 30 HK2 catalyzes the first step of most glucose metabolism pathways by phosphorylating glucose to produce glucose-6-phosphate. The GLUT1 and HK2 protein levels were increased in patients with GDM (n = 31) compared with those in healthy controls (n = 20), and miR-9 and miR-22 levels were reduced.…”

“… 23 , 31 Inhibitors of miR-9 and miR-22 enhanced viability and prevented apoptosis in primary syncytiotrophoblasts (STBs) and HTR-8/SVneo cells, which could be partially rescued by silencing GLUT1 and HK2. 30 …”

“…23,31 Inhibitors of miR-9 and miR-22 enhanced viability and prevented apoptosis in primary syncytiotrophoblasts (STBs) and HTR-8/SVneo cells, which could be partially rescued by silencing GLUT1 and HK2. 30 Additionally, Li et al 19 revealed that miR-345-3p expression decreased in GDM placentas and maternal blood (n = 30) compared with that in healthy controls (n = 30). Functional assays have shown that miR-345-3p overexpression could inhibit apoptosis and promote cell proliferation and migration in trophoblasts by targeting B-cell lymphoma 2 antagonist/killer 1 (BAK1), a member of the B-cell lymphoma 2 protein family involved in mitochondrial apoptosis.…”

circMAP3K4 regulates insulin resistance in trophoblast cells during gestational diabetes mellitus by modulating the miR-6795-5p/PTPN1 axis

“…For example, miR-140-3p was upregulated in the placentas of GDM patients, and was found to contribute to insulin signaling pathway impairment by directly targeting the insulin receptor and the insulin-like growth factor 1 receptor, inhibiting glucose uptake in HTR-8/SVneo and human umbilical vein endothelial cells [ 12 ]. At the same time, miR-9 and mir-22 expression levels were decreased in the placentas of GDM patients; miR-9 and mir-22 depletion promoted glucose uptake and lactate secretion in primary syncytiotrophoblast and HTR-8/SVneo cells by targeting glucose transporter 1 and hexokinase-2 [ 22 ]. Based on the ceRNA theory, circRNA may contribute to the regulation of placental signaling pathways through miRNA sponging and the subsequent reversal of its repressive effects on downstream genes.…”