MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2

Yuan, Yuan; Wang, Xiaoying; Sun, Qiuyu; Xu, Daohua; Cai, Yan

doi:10.1002/jcp.29330

Cited by 20 publications

(12 citation statements)

References 32 publications

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“…NOTCH2 and NOTCH3 signaling antagonize each other in different cell systems [56][57][58][59], suggesting that these NOTCH receptors also have opposite functions in the antigen-dependent regulation of CD5+ (B-1a) B-cell homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…The NOTCH3 gene is frequently epigenetically silenced in B-cell acute lymphocytic leukemia (B-ALL) cells, pointing to a broader tumor-suppressor role of NOTCH3 in B-cells [63]. Moreover, the CLL downregulated/deleted MicroRNA-16 [64] has been shown to exert its pro-apoptotic function by NOTCH2 inhibition in pre-eclampsia, where an inverse correlation between NOTCH2 and NOTCH3 expression also has been found [59].…”

Section: Discussionmentioning

confidence: 99%

“…NOTCH2 and NOTCH3 signaling antagonize each other in different cell systems [ 56 , 57 , 58 , 59 ], suggesting that these NOTCH receptors also have opposite functions in the antigen-dependent regulation of CD5+ (B-1a) B-cell homeostasis. Under physiological conditions, NOTCH2 signaling might be induced by ligand-expressing surrounding cells in order to protect the proliferative/regenerative reservoir of CD5+ B-cells from NR4A1-mediated activation-induced cell death (AICD) [ 32 , 52 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

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Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL

Hubmann

Schnabl

Araghi

et al. 2020

Cells

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NOTCH signaling represents a promising therapeutic target in chronic lymphocytic leukemia (CLL). We compared the anti-neoplastic effects of the nuclear NOTCH2 inhibitor gliotoxin and the pan-NOTCH γ-secretase inhibitor RO4929097 in primary CLL cells with special emphasis on the individual roles of the different NOTCH receptors. Gliotoxin rapidly induced apoptosis in all CLL cases tested, whereas RO4929097 exerted a variable and delayed effect on CLL cell viability. Gliotoxin-induced apoptosis was associated with inhibition of the NOTCH2/FCER2 (CD23) axis together with concomitant upregulation of the NOTCH3/NR4A1 axis. In contrast, RO4929097 downregulated the NOTCH3/NR4A1 axis and counteracted the spontaneous and gliotoxin-induced apoptosis. On the cell surface, NOTCH3 and CD23 expression were mutually exclusive, suggesting that downregulation of NOTCH2 signaling is a prerequisite for NOTCH3 expression in CLL cells. ATAC-seq confirmed that gliotoxin targeted the canonical NOTCH signaling, as indicated by the loss of chromatin accessibility at the potential NOTCH/CSL site containing the gene regulatory elements. This was accompanied by a gain in accessibility at the NR4A1, NFκB, and ATF3 motifs close to the genes involved in B-cell activation, differentiation, and apoptosis. In summary, these data show that gliotoxin recovers a non-canonical tumor-suppressing NOTCH3 activity, indicating that nuclear NOTCH2 inhibitors might be beneficial compared to pan-NOTCH inhibitors in the treatment of CLL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL

Hubmann

Schnabl

Araghi

et al. 2020

Cells

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“…Differentially expressed miRNAs have been found in exosomes [ 50 , 64 , 103 , 112 ] and Mesenchymal stem cells (MSCs) [ 28 , 51 , 71 , 76 ] as well as in placental tissues and peripheral serum or plasma. For example, miR-16 upregulation was first confirmed in the placentas of patients with PE [ 29 ]. Studies have shown that miR-16 is differentially expressed in the decidual MSCs of patients with severe PE and normal patients, and can inhibit the proliferation and migration of decidual-derived MSCs by targeting cyclin E1 and inducing cell cycle arrest [ 28 ].…”

Section: Mirnas and Preeclampsiamentioning

confidence: 99%

“… [ 18 – 23 ] miR-182-5p placenta upregulated RND3 the increased miRNA-182-5p expression could inhibit the migratory and invasive ability of trophoblast cells through targeted degrading RND3 protein [ 24 ] miR-155 placenta/placenta-associated serum exosomes upregulated CYR61/Cyclin D1 Overexpression of miR-155 in HTR-8/SVneo cells inhibited cell invasion, proliferation and increased cell number at the G1 stage in trophoblast cells [ 16 , 25 ] miR-155-5p placenta upregulated eNOS miR-155 inhibited cell invasion in trophoblast cells, and the effect was rescued by over expression of eNOS. [ 26 ] miR-195 placenta downregulated ActRIIB/ActRIIA miR-195 could promote cell invasion via directly targeting ActRIIB/ActRIIA in human trophoblast cells [ 27 ] miR-16 placenta/mesenchymal stem cell (MSC) upregulated CCNE1 /VEGF-A/Notch2 over-expressed miR-16 inhibited the proliferation and migration of decidua-derived mesenchymal stem cells /BeWo and JEG-3 cells, and induced cell-cycle arrest by targeting cyclin E1 [ 28 , 29 ] miRNA-376c placenta/plasma/exosome downregulated ALK5/ALK7/25-OH-VD miR-376c inhibits both ALK5 and ALK7 expression to impair transforming growth factor-β/Nodal signaling, leading to increases in cell proliferation and invasion [ 30 , 31 ] miR-29b decidua-derived mesenchymal stem cell (dMSC)/placenta upregulated MMP2/MCL1/ VEGFA/ ITGB1/HDAC4 miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. [ 32 ] miR-101 placenta downregulated ERp44/BRD4/CXCL6 miR-101 could promote apoptosis and inhibite the proliferation and migration of...…”

Section: Mirnas and Preeclampsiamentioning

confidence: 99%

Roles of noncoding RNAs in preeclampsia

Sun

Qin

Zhang

et al. 2021

Reprod Biol Endocrinol

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Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the “junk” of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

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The downregulation of miR‐22 and miR‐372 may contribute to gestational diabetes mellitus through regulating glucose metabolism via the PI3K/AKT/GLUT4 pathway

Li¹,

Yuan

et al. 2022

Clinical Laboratory Analysis

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Background: Identifying effective regulatory mechanisms will be significant for Gestational diabetes mellitus (GDM) diagnosis and treatment. Methods:The expressions of miR-22 and miR-372 in placenta tissues from 75 pregnant women with GDM and 75 matched healthy controls and HRT8/SVneo cells (a model of insulin resistance) were analyzed by qPCR. The expressions of PI3K, AKT, IRS, and GLUT4 in high glucose-treated HRT8/SVneo cells transfected with miR-22 or miR-372 mimics or inhibitors was assessed by Western blot. A luciferase gene reporter assay was employed to verify miRNAs' target genes. Results:The expressions of miR-22 and miR-372 in placental tissues from GDM patients and HRT8/SVneo cells were significantly decreased compared with the respective controls. The GLUT4 expression was significantly decreased in the placenta tissues of GDM and HRT8/SVneo cells with high glucose transfected with miR-22 and miR-372 inhibitors. We confirmed that SLC2A4, the gene encoding GLUT4, was a direct target of miR-22 and miR-372. In this study, we report that the lower expressions of miR-22 and miR-372 in placental tissue from GDM patients. Conclusion:Our results further suggested that the downregulations of miR-22 and miR-372 may contribute to GDM through regulating the PI3K/GLUT4 pathway.

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MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2

Abstract: In recent years, the role of microRNAs (miRNAs) in pre-eclampsia (PE) has been demonstrated, while the relevant mechanisms of miR-16 in PE await to be unearthed.

Cited by 20 publications

References 32 publications

Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL

Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL

Roles of noncoding RNAs in preeclampsia

The downregulation of miR‐22 and miR‐372 may contribute to gestational diabetes mellitus through regulating glucose metabolism via the PI3K/AKT/GLUT4 pathway

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