<p>Down-Regulated miR-21 in Gestational Diabetes Mellitus Placenta Induces PPAR-α to Inhibit Cell Proliferation and Infiltration</p>

Abstract

This study aimed to investigate the role of miR-21 expression in the reduction of placental function in GDM patients. Materials and Methods: qRT-PCR was used to detect the differential expression of miR-21 in the serum of gestational diabetes mellitus (GDM) and normal pregnant women, and to verify the functional target gene PPAR-α of miR-21 by double fluorescence experiments. Cellular experiments were performed to verify the effect of PPAR-α on cell function. Results: miR-21 is down-regulated in the serum and placenta of GDM patients compared to normal pregnant women. In the case of insulin resistance, miR-21-5p knockdown promoted glucose uptake, but no significant effect was found under physiological condition. Functional studies have shown that reduced PPAR-α expression can restore miR-21 knockdownmediated cell growth and metastasis inhibition. Additionally, decreased expression of miR-21 but increased expression of-PPAR-α was observed in patients with GDM and GDM rats. Conclusion: The expression of the placental miR-21-5p, which inhibits cell growth and infiltration by up-regulating PPAR-α, is downregulated in pregnant GDM patients, which in turn may affect the placental function.

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

“…33 miR-518d and miR-21-5p were dysregulated in GDM placentas and both were negatively correlated with the protein levels of their predicted target gene, PPARα. [34][35][36] Notably, the trend of PPAR-α protein levels in GDM placental tissue compared with that in the controls was inconsistent in these two studies, possibly due to the sample sizes and different populations. miR-518d is a member of the placentaspecific miRNA cluster, C19MC, and is located on chromosome 19q13.42.…”

“… 34 miR-21, located on chromosome 17q23.1, has attracted much attention as an important molecule related to tumors and diabetes. 35 A more recent study demonstrated a negative correlation between placental miR-21-5p and PPAR-α expression in 295 patients (GDM:control = 137:158). 35 The authors found that the serum expression of miR-21 in patients with GDM and GDM rat models was lower than that in the controls, and that miR-21 expression in GDM rats decreased with an increase in blood glucose concentration, suggesting that miR-21 is an indicator of GDM development.…”

“… 75 The miR-21 mimic transfected into HTR8/SVneo cells promoted cell proliferation, migration, and infiltration and inhibited apoptosis; the opposite effects were observed in the miR-21 inhibitor group. 35 The overexpression of miR-137 and miR-138 suppressed the viability and migration of HTR-8/SVneo cells, whereas miR-138 knockdown promoted cell migration and proliferation. 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.…”

Protection against Glucolipotoxicity by High Density Lipoprotein in Human PANC-1 Hybrid 1.1B4 Pancreatic Beta Cells: The Role of microRNA

“…Consequently, HDL-induced changes in miR-21-5p expression noted in the microchip array were confirmed by Q-PCR (Figure 5A): using this methodology, an increase due to HDL (63%; p < 0.05), but not apoA-I, was noted. Treatment The elevation of hsa-miR-21-5p in 1.1B4 cells detected by microchip analyses was of particular interest as this sequence and it targets have been associated with increased proliferation and reduced apoptosis [42][43][44][45][46], beta cell number and function [47][48][49] and the aetiology of diabetes [50][51][52][53][54]. Consequently, HDL-induced changes in miR-21-5p expression noted in the microchip array were confirmed by Q-PCR (Figure 5A): using this methodology, an increase due to HDL (63%; p < 0.05), but not apoA-I, was noted.…”

Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus

“…Similarly, miR-193b was downregulated in GDM patients, while an in vitro study found that its aberrantly low expression in high glucose (HG)-induced trophoblasts led to cell apoptotic events by upregulating insulin-like growth factor binding protein (IGFBP5)-induced autophagy, which might result in GDM ( 92 ). In addition, miR-21 was down-regulated in the sera and placentas of GDM patients compared to healthy pregnant women, and thus inhibited cell growth and infiltration by up-regulating PPAR-α ( 83 ). In addition, miR-29b expression was lower in placentas derived from patients with GDM than those in the control group ( 84 ).…”