Dataset Information

The Role of circRNA-SETD2/miR-519a/PTEN Axis in Fetal Birth Weight through Regulating Trophoblast Proliferation.

ABSTRACT: Abnormal birth weight is the one of the major causes of adulthood diseases such as obesity, metabolic syndrome, cardiovascular disease, type 2 diabetes, and hypertension. Accumulating evidence has suggested that the placental trophoblast is one of the most important reasons that influence birth weight. Our previous study showed that miR-519a are correlated with low fetal birth weight through regulating trophoblast proliferation. To further clarify the detailed mechanisms on how it is regulated, we screened the placental-specific circular RNAs (circRNAs) via microarray assay. The result identified that circ-SETD2 was highly expressed in the placenta of the patients with fetal macrosomia compared with healthy donors. Furthermore, bioinformatic analyses and the luciferase reporter assay revealed that miR-519a possessing the binding sites for both circ-SETD2 and phosphate and tensin homolog was deleted on chromosome 10 (PTEN). Interestingly, upregulation of circ-SETD2 enhanced the proliferation and invasion of the human trophoblast-like cell line HTR8/SVneo cell. A parallel study performed by Western blotting showed that overexpression of circ-SETD2 reduced miR-519a levels and increased PTEN levels in HTR8/SVneo cells. Importantly, the enhancement of HTR8/SVneo cell activity by circ-SETD2 overexpression was nullified when the cells were cotransfected by circ-SETD2 and miR-519a, suggesting the involvement of the circ-SETD2/miR-519a/PTEN axis in trophoblast activity. Taken together, we illustrate the role of circ-SETD2, as an upstream signaling of miR-519a/PTEN, in placenta development via regulating trophoblast proliferation and invasion. These findings improve our understanding of the mechanisms of progression of fetal macrosomia and will guide future development of therapeutic strategies against the disease by targeting the circ-SETD2/miR-519a/PTEN axis.

SUBMITTER: Wang D

PROVIDER: S-EPMC7306081 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Role of circRNA-SETD2/miR-519a/PTEN Axis in Fetal Birth Weight through Regulating Trophoblast Proliferation.

Wang Dan D Na Quan Q Song Guiyu G Wang Ying Y Wang Yang Y

BioMed research international 20200612

Abnormal birth weight is the one of the major causes of adulthood diseases such as obesity, metabolic syndrome, cardiovascular disease, type 2 diabetes, and hypertension. Accumulating evidence has suggested that the placental trophoblast is one of the most important reasons that influence birth weight. Our previous study showed that miR-519a are correlated with low fetal birth weight through regulating trophoblast proliferation. To further clarify the detailed mechanisms on how it is regulated, ...[more]

PMID: 32626774

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Project description:ContextDysregulated immune hemostasis occurs in unexplained recurrent spontaneous abortion (URSA). Synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), hydrogen sulfide (H2S) promotes regulatory T-cell differentiation and regulates immune hemostasis; yet, its role in URSA is elusive.ObjectiveTo determine if H2S plays a role in early pregnancy and if dysregulated H2S signaling results in recurrent spontaneous abortion.DesignFirst trimester placenta villi and decidua were collected from normal and URSA pregnancies. Protein expression was examined by immunohistochemistry and immunoblotting. Human trophoblast HTR8/SVneo and JEG3 cells were treated with H2S donors; HTR8/SVneo cells were transfected with CBS ribonucleic acid interference (RNAi) or complementary deoxyribonucleic acid. Cell migration and invasion were determined by transwell assays; trophoblast transcriptomes were determined by RNA sequencing (RNA-seq). Wild-type, CBS-deficient, and CBA/J × DBA/2 mice were treated with CBS and CSE inhibitors or H2S donors to determine the role of H2S in early pregnancy in vivo.ResultsCBS and CSE proteins showed cell-specific expressions, but only CBS decreased in the villous cytotrophoblast in URSA versus normal participants. H2S donors promoted migration and invasion and MMP-2 and VEGF expression in human placenta trophoblast cells that contain SV40 viral deoxyribonucleic acid sequences (HTR8/SVneo) and human placenta trophoblast cells (JEG3 cells), similar to forced CBS expression in HTR8/SVneo cells. The CBS-responsive transcriptomes in HTR8/SVneo cells contained differentially regulated genes (ie, interleukin-1 receptor and prostaglandin-endoperoxide synthase 2) that are associated with nuclear factor-κB-mediated inflammatory response. In vivo, dysregulated CBS/H2S signaling significantly increased embryonic resorption and decidual T-helper 1/T-helper 2 imbalance in mice, which was partially rescued by H2S donors.ConclusionCBS/H2S signaling maintains early pregnancy, possibly via regulating maternal-fetal interface immune hemostasis, offering opportunities for H2S-based immunotherapies for URSA.

Dataset Information

The Role of circRNA-SETD2/miR-519a/PTEN Axis in Fetal Birth Weight through Regulating Trophoblast Proliferation.

Publications

The Role of circRNA-SETD2/miR-519a/PTEN Axis in Fetal Birth Weight through Regulating Trophoblast Proliferation.

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