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

Abstract

Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.

Recent Updates on microRNA as Potential Biomarkers for Diagnosis of Gestational Diabetes Mellitus

“…Furthermore, pre-miRNA is transported into the cytoplasm by exportin 5, a nuclear export transporter that processes a 22-nucleotide "miRNA duplex" by engaging with the RNase III endonuclease dicer protein and a cofactor which is an RNA binding protein having doublestrands with responsiveness to transactivation. After binding to an argonaute and glycine tryptophan repeatcontaining protein, the miRNA duplex is integrated into an "RNA-induced silencing complex," where it attaches to partial or full-complementary sequences in the 3' untranslated region (3'-UTR) or 5'-UTR of the target mRNA, and thus participates in the regulatory gene expression procedure 7,12 . The process of miR biogenesis is displayed as a schematic in Figure 1.…”

“…Approximately 10-12 miR expression is linked with GDM. MicroRNA-9, -27a, -33a, -92a, -30d, -137, -362-5p and -502-5p were increased in placental tissues, while miR-132, -29a, and -222 expression was significantly downregulated in serum samples of patients with GDM [7][8][9] . The miRNA-16-5p, -17-5p, -19a-3p, -19b-3p and-20a-5p expression were seen to be increased in plasma samples of women during 16-19 weeks of pregnancy 10 .…”

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

“…Extracellular vesicles can provide some of this regulation by way of membrane-bound proteins and miRNAs. However, the discussion surrounding fetal regulation by extracellular vesicles is an emerging field and has been reviewed elsewhere (see [ 44 , 45 ]).…”

Long Non-Coding RNA Signatures in Lymphopoiesis and Lymphoid Malignancies

“…LncRNAs are an important class of non-coding RNAs that have been discovered in recent years. They have been implicated in a wide range of cellular processes and in the development of various diseases, including cancer, immune diseases, diabetes, and cardiovascular diseases [ 8 , 9 , 10 , 11 , 12 ]. According to the Human GENCODE statistics, the lncRNAs of the human genome are estimated to be approximately 19,000 genes [ 13 ], most of which are transcribed by RNA polymerase II and often have a polyadenylated tail at their 3′ ends and 7-methyl guanosine (m7G) caps at their 5′ ends [ 14 ].…”