Epigenetic regulation of folate receptor-α (FOLR1) in human placenta of preterm newborns

Piñuñuri, Raúl; Castaño-Moreno, Erika; Llanos, Miguel; Ronco, Ana María

doi:10.1016/j.placenta.2020.03.009

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…In the placenta, FRα transports folates from the mother to the fetus ( 30 , 31 ). Folate deficiency in pregnancy is associated with neural tube defects, restricted fetal growth and fetal programming of diseases later in life ( 32 – 34 ). Importantly, the risk of abnormal pregnancy outcomes is increased in pregnant women taking folate antagonists to treat cancer and other diseases.…”

Section: The Role Of Frα In Healthmentioning

confidence: 99%

Therapeutic strategies targeting folate receptor α for ovarian cancer

Mai,

Wu,

Yang

et al. 2023

Front. Immunol.

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Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.

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Section: The Role Of Frα In Healthmentioning

confidence: 99%

Therapeutic strategies targeting folate receptor α for ovarian cancer

Mai,

Wu,

Yang

et al. 2023

Front. Immunol.

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“… No association between homocysteine and methylation was investigated. 4 Pinunuri (2020) – Chile [ 46 ] Case-controls from prospective cohort Term ( n =16) and preterm (gestational age 32–36 weeks, n =23) deliveries in healthy women Folate and vitamin B 12 in umbilical cord blood Gene specific: CpG island upstream of transcription initiation site FOLR1 —MS-HRM Chorionic and basal plates biopsies near cord insertion Cord blood folate associated with FOLR1 methylation in the chorionic plate (Rho =0.665, p ≤0.05) but not in the basal plate. There were no associations between cord blood vitamin B 12 and FOLR1 methylation.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, this review shows that there is a lot of heterogeneity among studies regarding investigated exposures, studied outcomes, sample size, and study design. Additionally, differences in DNA methylation have been found between female and male offspring [ 35 ], depending on which part of the placenta was sampled [ 52 ], timing of exposure [ 32 , 37 ], and underlying genotype [ 42 ], which could also explain parts of observed differences between studies. Based on the use of ErasmusAGE quality score, we discussed studies with a quality score of at least 5 out of 10 points.…”

Section: Discussionmentioning

confidence: 99%

The one-carbon metabolism as an underlying pathway for placental DNA methylation – a systematic review

van Vliet,

Schoenmakers,

Gribnau

et al. 2024

Epigenetics

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Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B 12 provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 ( n = 15) and in vitro studies ( n = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation ( n = 9), (2) genome-wide analyses ( n = 4), and (3) gene specific ( n = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including LEP , NR3C1, CRH , and PlGF ; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.

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“…CEBPB (CCAAT enhancer binding protein beta) [38], ACSL4 [39], MBD2 [40], ULK1 [41], NUCB2 [42], TWIST1 [43], HOOK2 [44], CLDN7 [45], TBK1 [46], YIPF6 [47], TFRC (transferrin receptor) [48], ENPP2 [49], SLIT2 [50], MFGE8 [51], FAT1 [52], GPC4 [53], COL6A3 [54], EGFL6 [55], AOC3 [56], CCN2 [57], LYVE1 [58], RARA (retinoic acid receptor alpha) [59], COL18A1 [60], THY1 [61], CD36 [62], PEMT (phosphatidylethanolamine N-methyltransferase) [63], AIF1L [64], OXTR (oxytocin receptor) [65], LMNA (lamin A/C) [66], CXCL14 [67], DKK3 [68], ANGPTL2 [69] and CMTM7 [70] were reported to be associated with obesity, but these genes might be linked with progression of GDM. AHR (aryl hydrocarbon receptor) [71], STS (steroid sulfatase) [72], PLAC1 [73], CYP11A1 [74], PSG11 [75], STAT5B [76], TLR3 [77], FOLR1 [78], HSPB1 [79], HSP90AA1 [80], ANXA4 [81], ATF3 [82], DAPK1 [83], ENTPD1 [84], ABL1 [85], VSIG4 [86], CD99 [87], VWF (von Willebrand factor) [88], PODXL (podocalyxin like) [89], PDPN (podoplanin) [90], RND3 [91], VCAN (versican) [92], AXL (AXL receptor tyrosine kinase) [93], PIEZO1 [94], GAS6 [93], LAMA4 [95], CAV1 [96], DLL1 [97], CD44 [98], CD81 [99], SMAD3 [100], NES (nestin) [101], DCN (decorin) [102], AGTR1 [103], SLIT3 [104], B2M [105], STAT3 [106], STC1 [107] and ADAMTS1 [108] were shown to participate in facilitating the preeclampsia. Majchrzak-Celiń ka et al [109] ...…”

Section: Discussionmentioning

confidence: 99%

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

Vastrad¹,

Vastrad²,

Tengli

2021

Preprint

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Gestational diabetes mellitus (GDM) is one of the metabolic diseases during pregnancy. The identification of the central molecular mechanisms liable for the disease pathogenesis might lead to the advancement of new therapeutic options. 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 with limma package. Gene ontology (GO) and REACTOME 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 by the miRNet database and NetworkAnalyst database. 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. Biological process analysis of GO enrichment analysis showed these DEGs were mainly enriched in reproduction, nuclear outer membrane-endoplasmic reticulum membrane network, identical protein binding, cell adhesion, supramolecular complex and signaling receptor binding. Signaling pathway enrichment analysis indicated that these DEGs played a vital in cell surface interactions at the vascular wall and extracellular matrix organization. Ten genes, HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA in the center of the PPI network, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network were associated with GDM, according to ROC analysis. Finally, the most significant small molecules were predicted based on molecular docking. Our results indicated that HSP90AA1, EGFR, RPS13, RBX1, PAK1, FYN, ABL1, SMAD3, STAT3, and PRKCA could be the potential novel biomarkers for GDM diagnosis, prognosis and the promising therapeutic targets. The current might be essential to understanding the molecular mechanism of GDM initiation and development.

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Epigenetic regulation of folate receptor-α (FOLR1) in human placenta of preterm newborns

Cited by 9 publications

References 37 publications

Therapeutic strategies targeting folate receptor α for ovarian cancer

Therapeutic strategies targeting folate receptor α for ovarian cancer

The one-carbon metabolism as an underlying pathway for placental DNA methylation – a systematic review

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

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