Identification of miR-9 as a negative factor of insulin secretion from beta cells

Abstract

MicroRNA is a novel class of small noncoding RNA that has been implicated in a variety of physiological and pathological processes, including glucose homeostasis and diabetes mellitus. So far, a few studies have reported that miRNAs may be an important regulator in glucose-stimulated insulin secretion (GSIS) pathway. However, the role of miRNAs in this process remains unclear. The levels of miRNAs in mouse islets and MIN6 cells were determined by quantitative RT-PCR. Concentration of insulin was determined by ELISA, and the expression of the target protein was determined with western blot assay. The overexpression and downregulation of miRNAs in MIN6 were conducted using cell transfection methods. And luciferase assay was used to measure the direct interaction between miRNAs and target messenger RNAs 3'UTR. miR-9 was screened out for it was downregulated under the effects of short-term high glucose, while long-term high glucose relatively increased miR-9 expression. The Stxbp1 expression was decreased with the overexpression of miR-9 in MIN6 cells and increased when miR-9 was downregulated. Moreover, it was verified by luciferase assay that miR-9 regulated Stxbp1 gene expression by directly targeting Stxbp1 messenger RNA 3'UTR. This study suggests that the pathway consisting of miR-9 and Stxbp1 plays a key role in β-cell function, thus contributing to the network of miRNA-insulin secretion and offering a new candidate for diabetes therapy.

High Glucose Concentrations Negatively Regulate the IGF1R/Src/ERK Axis through the MicroRNA-9 in Colorectal Cancer

“…Several studies have provided sufficient evidence that miR-9 serves as a tumor suppressor in CRC [19,20,56]. Moreover, miR-9 has been implicated in insulin secretion and has been proposed to be regulated by HG levels in pancreatic beta-cells (insulinoma) [57,58], and recent works show that miR-9a regulates body growth by controlling sNPFR1/NPYR-mediated modulation of insulin signaling [59]. MiR-9 is considered a crucial mediator in cancer development; it works through various biological mechanisms to regulate various targets.…”

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

“…The suppression of miR-375 also appears to be the way of enhancing chondrocytes for antagonizing OxS in the course of osteoarthritis [154]. Other miRNAs such as miR-29a/c and miR-9 also control insulin release [155,156]. miR-9, an inflammation-associated miRNA, was indicated to participate in glucose-induced insulin secretion (GIIS) while repressing the expression of syntaxin-binding protein 1 (STXBP1) gene.…”

“…miR-9, an inflammation-associated miRNA, was indicated to participate in glucose-induced insulin secretion (GIIS) while repressing the expression of syntaxin-binding protein 1 (STXBP1) gene. The latter takes part in fusing insulin secretory granules with plasma membrane of β-cells [156]. Another study has indicated that miR-9 was induced by lipopolysaccharide (LPS) in a MyD88-and TLR4/NF-κB-dependent manner [157].…”

Circulating microRNA-7 regulates insulin, inflammatory and GnRH signaling pathways by targeting IRS1, IRS2, and RAF1 genes in gestational diabetes mellitus

“…Despite their classical role in mRNA interference, virtually miRNA plays a signi cant role in every cellular process, for example, proliferation, differentiation, apoptosis, and development. However, it is observed that over-expression or reduced expression of miRNAs (altered miRNAs) has been signi cantly correlated with many human diseases, including GDM [6,[12][13][14]. Although, the altered miRNAs and related target genes in placental tissue (PL), cord blood (CB), and maternal blood (MB) of GDM patients have never been investigated.…”