Integrated Transcriptome Sequencing Analysis Reveals Role of miR-138-5p/ TBL1X in Placenta from Gestational Diabetes Mellitus

Abstract

Background/Aims: The placenta has been suggested to play a crucial role in the pathology of gestational diabetes mellitus (GDM). Placenta-specific microRNAs (miRNAs) and the corresponding targeting genes involved in the pathology of GDM still remain to be elucidated. We aimed to identify the dysregulated miRNAs and the corresponding mRNA targets through an integrated miRNA and mRNA transcriptomic profiles analysis and investigate the role of differentially expressed miR-138-5p/TBL1X in GDM. Methods: RNA sequencing (RNA-seq) was performed in 16 placentas from GDM and control group. Differentially expressed mRNAs and miRNAs in GDM were validated by quantitative PCR (qPCR). The wound healing assay and transwell migration assay were used to analyze cell migration ability. The cell proliferation was determined by CCK8 assay. Luciferase assay was used to confirm the direct binding of the targeted TBL1X with miR-138-5p. Results: Totally, 281 mRNAs and 32 miRNAs were found to be differentially expressed in the GDM placentas. The biological relationships of the miRNA/mRNA pairs were related to cellular development and function and organ morphology. Among the aberrantly expressed molecules, we selected miR-138-5p from the bioinformatics analysis and found that miR-138-5p significantly inhibited the migration and proliferation of trophoblasts (HTR-8/SVneo) by targeting the 3’-UTR of TBL1X. Furthermore, the aberrant expression of miR-138-5p and TBL1X was significantly correlated with the weight of the placenta. Conclusion: We present the first integrative analysis of miRNA and mRNA expression profiles in GDM placenta and uncover a more detailed role for miR-138-5p, as well as its target TBL1X in the pathology of GDM.

Clinical application of exosomes and circulating microRNAs in the diagnosis of pregnancy complications and foetal abnormalities

“…Analysis of the circulating miRNA profiles in peripheral blood has revealed that miR-1275, miR-16-5p, miR-17-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-195-5p and miR-3664-3p are significantly upregulated in GDM pregnancies compared with those in normal pregnancies. In contrast, miR-29a, miR-132, miR-142-5p, miR-222 and miR-4666a-3p were found to be downregulated in women affected by GDM [51][52][53][54][55][56][57]. RNA sequencing has revealed that miR-138-5p is significantly downregulated in GDM placentas [53].…”

“…In contrast, miR-29a, miR-132, miR-142-5p, miR-222 and miR-4666a-3p were found to be downregulated in women affected by GDM [51][52][53][54][55][56][57]. RNA sequencing has revealed that miR-138-5p is significantly downregulated in GDM placentas [53]. A recent study reported that ten exosomal miRNAs in serum were present at significantly higher levels in GDM cases than in controls [56].…”

Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications

“…Ding et al uncovered a set of deregulated microRNAs by RNA sequencing and further qRT-PCR validation in placental tissues from eight GDM women compared to eight CTRLs [114]. An integrative evaluation of microRNA and mRNA expression was performed and the predicted biological functions of the differentially expressed microRNA and mRNA were related to placenta morphology and development.…”

Non-invasive prenatal testing reveals copy number variations related to pregnancy complications

“…Despite years of investigation, very little is known about the genetic predisposition for gestational diabetes mellitus (GDM). Increasing number of studies have reported pathological changes of placenta tissues in gestational diabetes mellitus (GDM), while the underlying mechanisms involved in this process are still largely uncertain [12, 13]. We herein tried to identify the genetic variation of placenta involving GDM currencies by the cell-free DNA in the maternal plasma, which was proved to be derived from placental trophoblast cells [14, 15].…”