MicroRNA-33a-5p sponges to inhibit pancreatic \u03b2-cell function in gestational diabetes mellitus LncRNA DANCR

Yan Feng,Xiaoyan Li,Yu Chen,Qi Feng,Jianwei Hu,Yinghong Zhang,Xin Qu

doi:10.1186/s12958-020-00618-8

Abstract

BackgroundGestational diabetes mellitus (GDM) is the most common medical complication associated with pregnancy, which may impose risks on both mother and fetus. Micro RNAs (miRNAs) and long noncoding RNAs (lncRNAs) are implied as vital regulators in GDM. A recent paper revealed dysregulation of miR-33a-5p in placental tissues of GDM patients. However, the biological function of miR-33a-5p in GDM remains elusive. This study focused on exploring the function and underlying mechanisms of miR-33a-5p in GDM.Methods12 GDM pregnancies and 12 healthy pregnancies were enrolled in the study. INS-1 cell line was applied in in vitro experiments. The expression levels of miR-33a-5p, lnc-DANCR (Differentiation Antagonizing Non-Protein Coding RNA), and ABCA1 (ATP-binding cassette transporter 1) mRNA were determined by RT-qPCR assay. Glucose and insulin levels were measured by ELISA assay. Luciferase reporter assay and western blot assay were applied to validate the target of miR-33a-5p.ResultsmiR-33a-5p was upregulated in the blood samples from GDM, and was positively correlated with blood glucose (p < 0.0001). Overexpression or inhibition of miR-33a-5p significantly inhibited or promoted cell growth and insulin production of INS-1 cells (p < 0.01). Furthermore, ABCA1 is a direct target of miR-33a-5p, and lnc-DANCR functions as a sponge for miR-33a-5p to antagonize the function of miR-33a-5p in INS-1 cells.ConclusionOur study demonstrated that lnc-DANCR-miR-33a-5p-ABCA1 signaling cascade plays a crucial role in the regulation of the cellular function of INS-1 cells.

Highlights

Gestational diabetes mellitus (GDM) is the most common medical complication associated with pregnancy, which may impose risks on both mother and fetus
Results miR-33a-5p and blood glucose levels were positively correlated in GDM Twelve blood samples from normal healthy pregnancies and 12 blood samples from GDM pregnancies were applied in the current study
To address the question of whether miR-33a-5p is involved in GDM, we compared the expression levels of miR-33a-5p between the two groups, and we found that the serum levels of miR-33a-5p were markedly upregulated in GDM compared with those in healthy donors (p < 0.01) (Fig. 1b)

Summary

Introduction

Gestational diabetes mellitus (GDM) is the most common medical complication associated with pregnancy, which may impose risks on both mother and fetus. Gestational diabetes mellitus (GDM) is a disease that women without diabetes have a high level of blood glucose during pregnancy [1]. Women with GDM are at the increased risk of development of type 2 diabetes, cardiovascular disease, and obesity [3, 4]. MiRNAs are recognized as vital regulators in various human diseases pathogenesis and progression [8], including GDM [9, 10]. MiRNAs participate in the regulation of GDM by affecting insulin production or endocrine pancreas development. MiR-9, an abundantly expressed miRNA in pancreatic islets, decreased the beta-cell secreted insulin upon glucose stimulation. MiR-7, a highly expressed miRNA in islets and pancreas, targets paired box 6 (Pax 6) to negatively regulate beta cells differentiation [12, 13]

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