Integrated bioinformatics analysis reveals novel key biomarkers and potential candidate small molecule drugs in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) is the metabolic disorder that appears during pregnancy. The current investigation aimed to identify central differentially expressed genes (DEGs) in GDM. The transcription profiling by array data (E-MTAB-6418) was obtained from the ArrayExpress database. The DEGs between GDM samples and non-GDM samples were analyzed. Functional enrichment analysis were performed using ToppGene. Then we constructed the protein–protein interaction (PPI) network of DEGs by the Search Tool for the Retrieval of Interacting Genes database (STRING) and module analysis was performed. Subsequently, we constructed the miRNA–hub gene network and TF–hub gene regulatory network. The validation of hub genes was performed through receiver operating characteristic curve (ROC). Finally, the candidate small molecules as potential drugs to treat GDM were predicted by using molecular docking. Through transcription profiling by array data, a total of 869 DEGs were detected including 439 up-regulated and 430 down-regulated genes. Functional enrichment analysis showed these DEGs were mainly enriched in reproduction, cell adhesion, cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3 and PRKCA were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. This investigation identified hub genes, signal pathways and therapeutic agents, which might help us, enhance our understanding of the mechanisms of GDM and find some novel therapeutic agents for GDM.

Integrated proteome and acetylome analyses unveil protein features of gestational diabetes mellitus and preeclampsia

“…Moreover, PE‐significantly regulated proteins only in the PE group were mainly enriched in the ribosome and fatty acid metabolism pathways. Some studies suggested dysregulation of ribosomal pathways in PE [24, 25]. Transcriptional profiling of the decidua in PE revealed fatty acid metabolism might play an essential role in pathogenesis [26, 27].…”

“…Alur et al. [24] revealed that HSP90AA1 were up‐regulated differentially expressed genes and were associated with GDM. And we also identified that the acetylation level of K209 on HSP90AA1 was increased in the GDM placentas.…”

“…Some studies suggested dysregulation of ribosomal pathways in PE [24,25]. Transcriptional profiling of the decidua in PE revealed fatty acid metabolism might play an essential role in pathogenesis [26,27].…”

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta

“…Through diverse in silico tools analyzing the interaction of gene/protein/miRNA/transcription factors, they described an important dysregulation of certain placental hormones, including leptin, insulin/IGF-I and their receptors, and the placental growth hormone receptor. Recently, other hormonal candidates that might play a role in the pathophysiology of GDM have been described through comprehensive bioinformatics, gene analysis, ROC analysis, and RT-PCR, including β-hCG, oxytocin receptors, binding proteins of IGF-I, and some cytochromes involved in the steroidogenic pathway [34,35].…”

Study of altered gut microbial dynamics and their association with gestational diabetes mellitus

“…During early gestation, the production of insulin is enhanced, while insulin sensitivity may or may not show any changes. However, during the later stages of pregnancy, female adipose tissue depots decline, whereas levels of post-prandial free fatty acids (FFAs) increase, and compared with pre-pregnancy, the glucose disposal mediated by insulin worsens by about 40-60% [19,27,34].…”