RETRACTED ARTICLE: miR-134-5p promotes inflammation and apoptosis of trophoblast cells via regulating FOXP2 transcription in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) is a prevalent and risky pregnant complication which warrants targeted therapy for restriction the inflammation and apoptosis of trophoblast cells. This study sought to analyze the aberrant expression and regulatory mechanism of microRNA (miR)-134-5p in GDM. The miR-134-5p expression in the serum of GDM patients and normal participants was detected via qRT-PCR, followed by receiver operating characteristic (ROC) curve analysis. In vitro GDM cell model was established in the HTR-8/SVneo cells using 25 mmol/L glucose, followed by transfection with miR-134-5p inhibitor and si-Forkhead box p2(FOXP2). The miR-134-5p and FOXP2 expressions, TNF-α, IL-1β, and IL-10 levels, cell proliferation, migration, and apoptosis were determined by a combination of qRT-PCR, western blot, ELISA, and cell counting Kit-8, Transwell assay, and flow cytometry. The binding relationship between miR-134-5p and FOXP2 was predicted and verified. Our results revealed that miR-134-5p was increased in the serum of GDM patients and could serve as a critical diagnostic marker for GDM. Moreover, miR-134-5p was upregulated in the high glucose (HG)-induced HTR-8/SVneo cells. The miR-134-5p inhibition suppressed the inflammation and apoptosis of HG-induced HTR-8/SVneo cells. miR-134-5p inhibited FOXP2 expression. FOXP2 expression was decreased in GDM. FOXP2 inhibition attenuated the function of miR-134-5p in HG-induced HTR-8/SVneo cells. Overall, miR-134-5p inhibited the FOXP2 expression to facilitate the inflammation and apoptosis of trophoblast cells, thereby exacerbating GDM.

Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

“…The 35 included studies ( Table 1 and Table 2 ) were evaluated using the Newcastle–Ottawa Scale (NOS) [ 15 , 54 ], with evaluation criteria listed in Supplementary Materials File S1 , and the NOS evaluations for each included study are displayed in Figure 2 . The average total NOS Score was 59%, ranging from 20% [ 47 ] to 90% [ 17 ]. The diagnosis of GDM was made using national guidelines or IADPSG criteria in 88% of studies (Criteria 3A), while none of the studies clearly described any loss of samples during experiments or data analysis (i.e., failed reactions, eliminated outliers, or absent values; Criteria 3C), although some studies did report number of subjects analyzed for each miRNA.…”

“…Patient characteristics were extracted from all included studies to investigate overall heterogeneity regarding included patients. Ten studies diagnosed GDM using IADPSG criteria [ 9 , 19 , 20 , 21 , 24 , 29 , 31 , 33 , 43 , 55 ], seven used ADA criteria [ 17 , 18 , 25 , 28 , 34 , 37 , 38 ], three used national guidelines [ 16 , 36 , 51 ], and one study used WHO criteria [ 22 ], while the remaining studies did not define GDM diagnosis according to any explicit diagnostic criteria ( Supplementary Materials; Data Extraction Sheet ). Patients were generally included with no specific reference to the BMI of patients and control subjects; however, four studies only investigated obese or overweight subjects [ 18 , 20 , 21 , 37 ], and one study only investigated subjects with a BMI < 25 kg/m 2 [ 23 ].…”

The Temporal Profile of Circulating miRNAs during Gestation in Overweight and Obese Women with or without Gestational Diabetes Mellitus

“…Most studies on circulating miRNAs in relation to GDM have only investigated the expression profile at a single time point in gestation [ 8 , 10 , 11 , 14 , 15 , 16 , 17 , 18 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], with the exception of one study [ 4 ]. There is limited consistency between the investigated miRNAs, although miR-16, -29a, -132, -223 and -330 are reported in more than one study.…”

“…Interestingly, the induction of miR-134-5p by hyperglycemia in vitro resulted in impaired cell migration and tube formation abilities in endothelial cell progenitors [ 52 ]. Elevated levels of miR-134-5p are associated with both GDM [ 7 , 40 ] and pre-eclampsia and the suppression of infiltration of trophoblast cells [ 53 ], suggesting that dysregulated miR-134 could contribute to GDM pathology. We observed that both miR-433-3p and miR-134-5p were positively associated with gestational weight gain.…”

Potential multi-modal effects of provirus integration on HIV-1 persistence: lessons from other viruses

“…Integrations of HPV and HBV sequences can induce the expression of prosurvival factors. For HBV, the RIG FOXP2 [66,67] encodes a transcription factor that contributes to preventing inflammation and apoptosis [94]. Similarly, primary oropharyngeal cancer cells show an HPV integration hotspot in intron 10 of BRISC and BRCA1 A complex member 2 (BABAM2) [35], a gene that blocks TNF-α-induced apoptosis [95].…”