MicroRNA-9 affects isolated ovarian granulosa cells proliferation and apoptosis via targeting vitamin D receptor

Kong, Fanzhi; Du, Chenxiang; Wang, Yu

doi:10.1016/j.mce.2019.02.012

Cited by 15 publications

(4 citation statements)

References 32 publications

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“…To explain the preferential effect of vitamin D on CD46-costimulated cells compared with CD28-activated cells, the levels of expression of VDR, CYP27B1 and CYP24A1 mRNA in activated T cells were assessed, with and without the addition of 1,25(OH)2D3 ( Figure 5). We also examined expression of the miRNA miR-9 that regulates VDR expression (48). Differences in their expression were found depending on the costimulatory signals received by the T cells.…”

Section: 25(oh)2d3 Favors Chemotaxis Of Cd46-mediated Tr1 Cells Towmentioning

confidence: 99%

Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

et al. 2020

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.

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Section: 25(oh)2d3 Favors Chemotaxis Of Cd46-mediated Tr1 Cells Towmentioning

confidence: 99%

Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

et al. 2020

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“…The ceRNA hypothesis enables the exploration of potential regulatory mechanisms by combining multiple RNA information (36). In this study, we identified 40 differentially expressed miRNAs (DEmiRNAs), 379 differentially expressed long non-coding RNAs (DElncRNAs), and 129 differentially expressed circular RNAs in the follicular fluid of PCOS patients, and its interaction with the vitamin D receptor modulates the proliferation and apoptosis of ovarian granulosa cells, thereby regulating follicle growth (38)(39)(40). Moreover, miR-9 increases during the ovarian development of tilapia, thereby affecting sex determination and differentiation by regulating dmrt1 expression (41).…”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome analysis revealed the regulatory network and related pathways of non-coding RNA regulating ovarian atrophy in broody hens

Xiong,

Li,

Wang

et al. 2024

Front. Vet. Sci.

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Poultry broodiness can cause ovarian atresia, which has a detrimental impact on egg production. Non-coding RNAs (ncRNAs) have become one of the most talked-about topics in life sciences because of the increasing evidence of their novel biological roles in regulatory systems. However, the molecular mechanisms of ncRNAs functions and processes in chicken ovarian development remain largely unknown. Whole-transcriptome RNA sequencing of the ovaries of broodiness and laying chickens was thus performed to identify the ncRNA regulatory mechanisms associated with ovarian atresia in chickens. Subsequent analysis revealed that the ovaries of laying chickens and those with broodiness had 40 differentially expressed MicroRNA (miRNAs) (15 up-regulated and 25 down-regulated), 379 differentially expressed Long Noncoding RNA (lncRNAs) (213 up-regulated and 166 down-regulated), and 129 differentially expressed circular RNA (circRNAs) (63 up-regulated and 66 down-regulated). The competing endogenous RNAs (ceRNA) network analysis further revealed the involvement of ECM-receptor interaction, AGE-RAGE signaling pathway, focal adhesion, cytokine-cytokine receptor interaction, inflammatory mediator regulation of TRP channels, renin secretion, gap junction, insulin secretion, serotonergic synapse, and IL-17 signaling pathways in broodiness. Upon further analysis, it became evident that THBS1 and MYLK are significant candidate genes implicated in the regulation of broodiness. The expression of these genes is linked to miR-155-x, miR-211-z, miR-1682-z, gga-miR-155, and gga-miR-1682, as well as to the competitive binding of novel_circ_014674 and MSTRG.3306.4. The findings of this study reveal the existence of a regulatory link between non-coding RNAs and their competing mRNAs, which provide a better comprehension of the ncRNA function and processes in chicken ovarian development.

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“…MicroRNAs (miRNAs) are a group of small non-coding RNAs that are involved in mediating RNA destabilization and/or inhibiting translation by binding partially complementary target mRNAs. The role of miRNA has been reported in regulating GCs function, oocyte maturation, follicle development and abnormal steroidogenesis in PCOS (9)(10)(11)(12)(13). Aberrant expression of miRNAs in GCs may contribute to the pathology of PCOS.…”

Section: Introductionmentioning

confidence: 99%

Let-7i Regulates KGN Proliferation and Estradiol Biosynthesis By Directly Targeting IMP2 in Polycystic Ovary Syndrome

Shen

et al. 2021

Preprint

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Background: Increased granulosa cell division is associated with abnormal folliculogenesis in polycystic ovary syndrome (PCOS). As the most abundant microRNA molecule in the development of follicles, let-7i was found to be differentially expressed in PCOS patients and controls. This study aimed to investigate the role of let-7i in PCOS and explore its related mechanisms.Methods: The expression of let-7i was measured in GCs from women with PCOS and without PCOS. An immortalized human granulose cell line, KGN, was used for the functional study. Let-7i mimics, let-7i inhibitors, lentiviruses expressing IMP2 and small-interfering RNA were transfected respectively into KGN cells. KGN cell proliferation was determined by an EdU assay kit and cck-8. Cell cycle and apoptosis were determined by PI staining and flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were utilized to evaluate genes expression. Estradiol biosynthesis was determined by ELISA analysis. Bioinformatics analysis and luciferase reporter assay were applied to confirm the target gene of let-7i.Results: let-7i was down-regulated in PCOS GCs. Let-7i mimics (150 nM) inhibited KGN proliferation, arrested cell cycle progression, and decreased aromatase expression and estradiol production, while the let-7i inhibitors (150 nM) had the opposite effect. Bioinformatics analysis and qRT-PCR identified IMP2 was a target of let-7i. QRT-PCR and western blot analysis indicated that IMP2 was up-regulated in PCOS GCs and the expression of IMP2 was suppressed by let-7i in KGN. The further luciferase reporter assay combined with rescue assay validated that let-7i inhibited KGN proliferation and estradiol production by directly targeting IMP2 mRNA.Conclusions: Let-7i was down-regulated in PCOS GCs. Let-7i overexpression inhibited KGN proliferation and decreased estradiol production in an IMP2-dependent manner, providing insights into the pathogenesis of PCOS.

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MicroRNA-9 affects isolated ovarian granulosa cells proliferation and apoptosis via targeting vitamin D receptor

Cited by 15 publications

References 32 publications

Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis

Whole transcriptome analysis revealed the regulatory network and related pathways of non-coding RNA regulating ovarian atrophy in broody hens

Let-7i Regulates KGN Proliferation and Estradiol Biosynthesis By Directly Targeting IMP2 in Polycystic Ovary Syndrome

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