Mesenchymal Progenitors Aging Highlights a miR-196 Switch Targeting HOXB7 as Master Regulator of Proliferation and Osteogenesis

Candini, Olivia; Spano, Carlotta; Murgia, Alba; Grisendi, Giulia; Veronesi, Elena; Piccinno, Maria Serena; Ferracin, Manuela; Negrini, Massimo; Giacobbi, Francesca; Bambi, Franco; Horwitz, Edwin M.; Conte, Pierfranco; Paolucci, Paolo; Dominici, Massimo

doi:10.1002/stem.1897

Cited by 54 publications

(52 citation statements)

References 62 publications

(107 reference statements)

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“…In addition, increased miR-196a in stem cells is associated with increased senescence [36]. Although not directly referred to RBCs, these evidence cannot be ignored, since it reveals an involvement of this miRNA in senescence pathways.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Dysregulation Associated with Red Blood Cell Storage

Chen

Xie

Xing

et al. 2018

Transfus Med Hemother

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Introduction: Stored red blood cells (RBCs) undergo storage lesions involving morphological, physiological and biochemical changes. MicroRNAs (miRNAs) have important functions in cell apoptosis and life processes. Therefore, the aim of this study was to explore potential roles of miRNAs in the damage of stored RBCs. Methods: Blood samples were collected from 13 healthy male O-type donors, and leuko-reduced RBCs were divided into fresh RBC group and 20-day storage RBC group. Results: Eight predicted miRNAs with modified expressions with an intersection ≥ 3 were found dysregulated in the 20-day storage RBC group and involved in apoptosis and senescence signaling pathway: miR-31-5p, miR-196a-5p, miR-203a, miR-654-3p and miR-769-3p were increased, while miR-96-5P, miR-150-5P and miR-197-3p were decreased. Evidence associating miR-31-5p, miR-203a, miR-654 and miR-769 to RBCs or blood in general are not available. Conclusions: Dysregulated miRNAs might represent potential biomarkers to identify storage lesions, and their detection might help to evaluate the quality of stored RBCs.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Dysregulation Associated with Red Blood Cell Storage

Chen

Xie

Xing

et al. 2018

Transfus Med Hemother

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“…MicroRNAs (miRNAs) play important roles in the regulation of cellular senescence [23, 24] and the pathogenesis of PE [25]. MiR-495 was reported as an anti-tumor miRNA which could inhibit cell migration, invasion and proliferation, thus to play negative roles in the carcinogenesis [26-29].…”

Section: Introductionmentioning

confidence: 99%

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

Song

Liú

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

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“…In turn, BMP signaling represses Hoxc8 activity through SMAD1 interaction with Hoxc8, relieving repression of osteopontin transcription. In addition to Hoxc8, miR-196a targets Hoxb7 in adult MSCs [79]. Over-expression of Hoxb7 enhances the proliferative and osteogenic capacity of MSCs.…”

Section: Mir-snps: Snps In Mirna Genes Altering Their Biogenesis Amentioning

confidence: 99%

MicroRNA variants as genetic determinants of bone mass

Dole

Delany

2016

Bone

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Single nucleotide polymorphisms (SNPs) are the most abundant genetic variants that contribute to the heritability of bone mass. MicroRNAs (miRNAs, miRs) are key post-transcriptional regulators that modulate the differentiation and function of skeletal cells by targeting multiple genes in same or distinct signaling pathways. SNPs in miRNA genes and miRNA binding sites can alter miRNA abundance and mRNA targeting. This review describes the potential impact of miRNA-related SNPs on skeletal phenotype. Although many associations between SNPs and bone mass have been described, this review is limited to gene variants for which a function has been experimentally validated. SNPs in miRNA genes (miR-SNPs) that impair miRNA processing and alter the abundance of mature miRNA are discussed for miR-146a, miR-125a, miR-196a, miR-149 and miR-27a. SNPs in miRNA targeting sites (miR-TS-SNPs) that alter miRNA binding are described for the bone remodeling genes bone morphogenetic protein receptor 1 (Bmpr1), fibroblast growth factor 2 (Fgf2), osteonectin (Sparc) and histone deacetylase 5 (Hdac5). The review highlights two aspects of miRNA-associated SNPs: the mechanism for altering miRNA mediated gene regulation, and the potential of miR-associated SNPs to alter osteoblast, osteoclast or chondrocyte differentiation and function. Given the polygenic nature of skeletal diseases like osteoporosis and osteoarthritis, validating the function of additional miRNA-associated SNPs has the potential to enhance our understanding of the genetic determinants of bone mass and predisposition to selected skeletal diseases.

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Mesenchymal Progenitors Aging Highlights a miR-196 Switch Targeting HOXB7 as Master Regulator of Proliferation and Osteogenesis

Cited by 54 publications

References 62 publications

MicroRNA Dysregulation Associated with Red Blood Cell Storage

MicroRNA Dysregulation Associated with Red Blood Cell Storage

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

MicroRNA variants as genetic determinants of bone mass

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