MeCP2-mediated epigenetic regulation in senescent endothelial progenitor cells

Wang, Chunli; Wang, Fei; Li, Zhen; Cao, Qing; Huang, Liya; Chen, Shuyan

doi:10.1186/s13287-018-0828-y

Cited by 24 publications

(18 citation statements)

References 40 publications

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“…MECP2 is most abundantly produced in the brain where it is expressed primarily in post-mitotic neurons [ 23 ]. Previous work has also shown MECP2 mediated epigenetic regulation of senescent endothelial progenitor cells and promoted apoptosis [ 24 ]. Furthermore, a recent study provides evidence that elevated MECP2 in mice causes neurodegeneration [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis

Mao

Byrum

Nishiyama

et al. 2018

IJMS

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Astronauts are reported to have experienced some impairment in visual acuity during their mission on the International Space Station (ISS) and after they returned to Earth. There is emerging evidence that changes in vision may involve alterations in ocular structure and function. To investigate possible mechanisms, changes in protein expression profiles and oxidative stress-associated apoptosis were examined in mouse ocular tissue after spaceflight. Nine-week-old male C57BL/6 mice (n = 12) were launched from the Kennedy Space Center on a SpaceX rocket to the ISS for a 35-day mission. The animals were housed in the mouse Habitat Cage Unit (HCU) in the Japan Aerospace Exploration Agency (JAXA) “Kibo” facility on the ISS. The flight mice lived either under an ambient microgravity condition (µg) or in a centrifugal habitat unit that produced 1 g artificial gravity (µg + 1 g). Habitat control (HC) and vivarium control mice lived on Earth in HCUs or normal vivarium cages, respectively. Quantitative assessment of ocular tissue demonstrated that the µg group induced significant apoptosis in the retina vascular endothelial cells compared to all other groups (p < 0.05) that was 64% greater than that in the HC group. Proteomic analysis showed that many key pathways responsible for cell death, cell repair, inflammation, and metabolic stress were significantly altered in µg mice compared to HC animals. Additionally, there were more significant changes in regulated protein expression in the µg group relative to that in the µg + 1 g group. These data provide evidence that spaceflight induces retinal apoptosis of vascular endothelial cells and changes in retinal protein expression related to cellular structure, immune response and metabolic function, and that artificial gravity (AG) provides some protection against these changes. These retinal cellular responses may affect blood–retinal barrier (BRB) integrity, visual acuity, and impact the potential risk of developing late retinal degeneration.

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Section: Discussionmentioning

confidence: 99%

Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis

Mao

Byrum

Nishiyama

et al. 2018

IJMS

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“…Similar to the connection between linc-ROR and angiogenesis, it has also been reported that miR-194 is a microRNA downstream of p53 that affects the expression of genes that regulates angiogenesis (Brumm et al, 2017), miR-194 is enriched by GO terms including angiogenesis in central nervous system lymphoma (Takashima et al, 2019) and could promote angiogenesis in hepatopulmonary syndrome (Chen et al, 2019) and in colon cancers (Sundaram et al, 2011). MECP2 can reduce the angiogenesis of senescent endothelial progenitor cells (EPCs) through SIRT1 promoter hypermethylation (Wang et al, 2018), and SIRT1 promotes angiogenesis by increasing VEGF expression (Balaiya et al, 2012). From the above, we can speculate that MECP2 can decrease the expression of mTOR to reduce angiogenesis, but miR-194 downregulates the expression of MECP2 to promote angiogenesis, thus increasing the sensitivity of breast cancer cells to rapamycin treatment.…”

Section: Linc-ror Promotes Cell Proliferation Migration and Invasiomentioning

confidence: 99%

Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2

et al. 2020

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linc‐ROR is reported to be a potential biomarker of breast cancer, but the detailed mechanism of linc‐ROR‐mediated breast cancer regulation has not been fully studied. We aimed to explore how linc‐ROR affects proliferation, metastasis, and drug sensitivity in breast cancer. Cell lines in which linc‐ROR was overexpressed or knocked down were constructed, and the cell proliferation, colony formation, cell migration, and invasion abilities of these lines were explored. A CCK‐8 assay was performed to determine the sensitivity of the breast cancer cells to rapamycin. Next‐generation sequencing was conducted to explore the detailed regulatory mechanism of linc‐ROR; differentially expressed RNAs in the linc‐ROR‐overexpressing cell line compared with the negative control were screened out, and their target genes were chosen to perform Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, protein–protein interaction network analysis, and competing endogenous RNA (ceRNA) network analysis. The ceRNA mechanism of linc‐ROR for miR‐194‐3p, which targets MECP2, was determined through dual‐luciferase reporter assay, RT–qPCR, western blot, and rescue experiments. Finally, we found that linc‐ROR was upregulated in breast tumor tissues. linc‐ROR promoted the cell proliferation, colony formation, cell migration, and invasion of breast cancer and decreased the sensitivity of breast cancer cells to rapamycin. The overexpression of linc‐ROR triggered changes in the whole transcriptome of breast cancer cells, and a total of 85 lncRNAs, 414 microRNAs, 490 mRNAs, and 92 circRNAs were differentially expressed in the linc‐ROR‐overexpressing cell line compared with the negative control. Through a series of bioinformatic analyses, the ‘linc‐ROR/miR‐194‐3p/MECP2’ ceRNA regulatory axis was confirmed to be involved in the linc‐ROR‐mediated progression and drug sensitivity of breast cancer. In conclusion, linc‐ROR serves as an onco‐lncRNA in breast cancer and promotes the survival of breast cancer cells during rapamycin treatment by functioning as a ceRNA sponge for miR‐194‐3p, which targets MECP2.

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“…1D ). Experimental results on senescent endothelial progenitor cells (EPCs) revealed that MeCP2 might moderate angiogenesis [ 107 ]. These analytical results suggest that the transcriptomic differences are closely related to the phenotypic sex differences in an animal model of MeCP2.…”

Section: Sex Difference In Genetic Models Of Autismmentioning

confidence: 99%

Sex-specific Behavioral Features of Rodent Models of Autism Spectrum Disorder

et al. 2018

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Sex is an important factor in understanding the clinical presentation, management, and developmental trajectory of children with neuropsychiatric disorders. While much is known about the clinical and neurobehavioral profiles of males with neuropsychiatric disorders, surprisingly little is known about females in this respect. Animal models may provide detailed mechanistic information about sex differences in autism spectrum disorder (ASD) in terms of manifestation, disease progression, and development of therapeutic options. This review aims to widen our understanding of the role of sex in autism spectrum disorder, by summarizing and comparing behavioral characteristics of animal models. Our current understanding of how differences emerge in boys and girls with neuropsychiatric disorders is limited: Information derived from animal studies will stimulate future research on the role of biological maturation rates, sex hormones, sex-selective protective (or aggravating) factors and psychosocial factors, which are essential to devise sex precision medicine and to improve diagnostic accuracy. Moreover, there is a strong need of novel strategies to elucidate the major mechanisms leading to sex-specific autism features, as well as novel models or methods to examine these sex differences.

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MeCP2-mediated epigenetic regulation in senescent endothelial progenitor cells

Cited by 24 publications

References 40 publications

Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis

Impact of Spaceflight and Artificial Gravity on the Mouse Retina: Biochemical and Proteomic Analysis

Linc‐ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR‐194‐3p targeting MECP2

Sex-specific Behavioral Features of Rodent Models of Autism Spectrum Disorder

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