The miR-29b–Sirt1 axis regulates self-renewal of mouse embryonic stem cells in response to reactive oxygen species

Xu, Zeng‐Guang; Zhang, Lei; Fei, Xuejie; Yi, Xingwen; Li, Wenxian; Wang, Qingxiu

doi:10.1016/j.cellsig.2014.03.010

Cited by 23 publications

(20 citation statements)

References 19 publications

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“…We further confirmed that miR-29b regulates SIRT1 by directly targeting its 3’UTR sequences, which adds a novel role for miR-29b as a ROS regulator in EOC development. Of note, our data are in agreement with previous reports demonstrating that miR-29s is capable of regulating SIRT1 in age-related hearing loss and self-renewal of mouse embryonic stem cells, adding a novel role of the tumor suppressor miRNA miR-29b in cancerous oxidative stress [24, 25]. Intriguingly, recent studies have observed a panel of differentially expressed miRNAs in urines of ovarian cancer patients as compared to healthy control [26].…”

Section: Discussionsupporting

confidence: 81%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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Background: Metabolic abnormalities are frequently observed in multiple malignancies including epithelial ovarian cancer (EOC), among which imbalance between generation and elimination of reactive oxygen species (ROS) plays a critical role in EOC onset and progression. Here we investigated the role of miR-29b, a well-established tumor-suppressor miRNA in metabolic regulation of EOC cells. Methods: cell viability and apoptosis in miR-29b inhibited and over-expressed EOC cells were evaluated by CCK8 and Annexin V–FITC/PI assays. Change in miR-29b was detected in EOC cells incubated in H₂O₂ culture by q-PCR. Relative ROS levels were also detected in different EOC cultures, including modified miR-29b and SIRT1 levels as well as H₂O₂ incubation. A luciferase reporter assay was employed to detect the direct binding of miR-29b to SIRT1 3’ UTR. Changes in cell viability and ROS levels were assessed in SIRT1-knocked down EOC cells. Results: miR-29b expression correlates with decreased EOC cell viability and increased apoptosis. H₂O₂ downregulated miR-29b in a time and dose-dependent manner. miR-29b expression negatively correlated with ROS levels, whereas SIRT1 significantly stimulated ROS formation. Luciferase reporter assays confirmed miR-29b downregulation of SIRT1by directly targeting its mRNA 3’-UTR. SIRT1 silencing rescues cell viability of H₂O₂ treated cells. Also, SIRT1 inhibition blocked cell apoptosis induced by H₂O₂ as well as reduced intracellular ROS levels. Conclusion: Together, our findings indicated that the miR-29b/SIRT1 axis has a protective effect against H₂O₂-induced damage of cell viability and oxidative stress and may provide novel options for miR-29b-based therapeutic approaches for EOC treatment.

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Section: Discussionsupporting

confidence: 81%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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“…In our study, SIRT1 was downregulated in FoEV-treated embryos, which could have been due to miR-29b-3p, which is found in bovine oEVs [19]. In mouse embryonic stem cells, Sirt1 has been identified as a direct target of miR-29b [67]. In addition to Sirt1, many more genes in the network were connected to the process "apoptosis of embryonic cell lines".…”

Section: Unveiling the Potential Of Oev Rna Components To Regulate Emmentioning

confidence: 54%

The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome

Bauersachs

Mermillod

Almiñana

2020

IJMS

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Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo–oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of embryonic gene expression, the transcriptomes of embryos supplemented with bovine fresh (FeEVs) or frozen (FoEVs) oEVs during in vitro culture compared to controls without oEVs were analyzed by low-input RNA sequencing. Analysis of RNA-seq data revealed 221 differentially expressed genes (DEGs) between FoEV treatment and control, 67 DEGs for FeEV and FoEV treatments, and minor differences between FeEV treatment and control (28 DEGs). An integrative analysis of mRNAs and miRNAs contained in oEVs obtained in a previous study with embryonic mRNA alterations pointed to direct effects of oEV cargo on embryos (1) by increasing the concentration of delivered transcripts; (2) by translating delivered mRNAs to proteins that regulate embryonic gene expression; and (3) by oEV-derived miRNAs which downregulate embryonic mRNAs or modify gene expression in other ways. Our study provided the first high-throughput analysis of the embryonic transcriptome regulated by oEVs, increasing our knowledge on the impact of oEVs on the embryo and revealing the oEV RNA components that potentially regulate embryonic development.

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“…Indeed, it is recently demonstrated that ROS modulates Oct-4 posttranslational modifications (such as sumoylation and ubiquitination), leading to the enhanced nuclear localization of Oct-4 [ 84 ]. Sirt-1, a key cell survival factor activated upon ROS exposure, is down-regulated during ROS-induced differentiation through the activity of miR-29b [ 85 ]. Sirt-1 also regulates the activation of FoXOs which are required to maintain pluripotency by directly regulating the expression levels of Oct-4, Nanog, and SOX-2 in human ESCs ( Figure 3(b) ) [ 86 , 87 ].…”

Section: Ros Regulates the Balance Between Self-renewal And Differmentioning

confidence: 99%

Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation

Sart

Song

2015

Oxidative Medicine and Cellular Longevity

121

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Reactive oxygen species (ROS) have long been considered as pathological agents inducing apoptosis under adverse culture conditions. However, recent findings have challenged this dogma and physiological levels of ROS are now considered as secondary messengers, mediating numerous cellular functions in stem cells. Stem cells represent important tools for tissue engineering, drug screening, and disease modeling. However, the safe use of stem cells for clinical applications still requires culture improvements to obtain functional cells. With the examples of mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), this review investigates the roles of ROS in the maintenance of self-renewal, proliferation, and differentiation of stem cells. In addition, this work highlights that the tight control of stem cell microenvironment, including cell organization, and metabolic and mechanical environments, may be an effective approach to regulate endogenous ROS generation. Taken together, this paper indicates the need for better quantification of ROS towards the accurate control of stem cell fate.

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The miR-29b–Sirt1 axis regulates self-renewal of mouse embryonic stem cells in response to reactive oxygen species

Cited by 23 publications

References 19 publications

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome

Controlling Redox Status for Stem Cell Survival, Expansion, and Differentiation

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