Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis

Bellavia, Daniele; Luca, Angela De; Carina, Valeria; Costa, Viviana; Raimondi, Lavinia; Salamanna, Francesca; Alessandro, Riccardo; Fini, Milena; Giavaresi, G.

doi:10.1016/j.bone.2019.02.013

Cited by 88 publications

(80 citation statements)

References 173 publications

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“…Despite this study focused on the effect of circFOXO3 on miR‐29a , we could reasonably hypothesize that circFOXO3 could also sponge miR‐29b/c . miR‐29b is a miRNA that regulates both osteoblastogenesis and osteoclastogenesis . Furthermore, serum miR‐29b is down‐regulated in PCa patients and this increases the formation of osteolytic lesions, influencing osteoblast and osteoclast differentiation and activities .…”

Section: Discussionmentioning

confidence: 99%

“…is a miRNA that regulates both osteoblastogenesis and osteoclastogenesis. 29 Furthermore, serum miR-29b is down-regulated in PCa patients and this increases the formation of osteolytic lesions, influencing osteoblast and osteoclast differentiation and activities. 30 These results suggested that overexpression in serum of circFOXO3 could influence osteolytic lesions formation through these processes in PCa.…”

Section: Discussionmentioning

confidence: 99%

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Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR‐29a‐3p

Kong

Wan

et al. 2019

J Cellular Molecular Medi

116

110

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Circular RNA FOXO3 (CircFOXO3, also termed as Hsa_circ_0006404) is derived from exon 2 of forkhead box O3 (FOXO3) gene, and abnormal expression is shown in different diseases. However, whether circFOXO3 plays important roles in tumorigenesis and progression of prostate cancer (PCa) remains unclear. In this study, we found that circFOXO3 was up‐regulated in both PCa tissues and serum samples. Moreover, circFOXO3 was positively correlated with the Gleason score in PCa samples. CircFOXO3 was observed to be up‐regulated in Gleason score > 6 PCa samples compared with Gleason score = 6 PCa samples. Knock‐down circFOXO3 could remarkably inhibit PCa cell cycle, proliferation and promote cell apoptosis in vitro. Furthermore, we demonstrated circFOXO3 could act as miR‐29a‐3p sponge to up‐regulate SLC25A15 expression by bioinformatics analysis, dual‐luciferase reporter assays and biotinylated RNA pull‐down assays. SLC25A15 could reverse the tumour suppressing roles of knock‐down circFOXO3 in PCa. Of note, we found that miR‐29a‐3p was down‐regulated; however, SLC25A15 was overexpressed in PCa samples compared with normal tissues. In conclusion, circFOXO3 acts as a miR‐29a‐3p sponge to exhibit oncogenic activity that affects the cell cycle and cell apoptosis in PCa through transcriptional up‐regulation of SLC25A15. Our analysis suggests circFOXO3 could act as promising prostate cancer biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR‐29a‐3p

Kong

Wan

et al. 2019

J Cellular Molecular Medi

116

110

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“…MiR-33 is a miRNA family that is highly conserved from Drosophila to humans [39]. Two isoforms of miR-33, miR-33a and miR-33b, are expressed in humans.…”

Section: Discussionmentioning

confidence: 99%

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Costa

Carina

Raimondi

et al. 2019

Cells

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Mesenchymal stromal cells (hMSCs) display a pleiotropic function in bone regeneration. The signaling involved in osteoblast commitment is still not completely understood, and that determines the failure of current therapies being used. In our recent studies, we identified two miRNAs as regulators of hMSCs osteoblast differentiation driving hypoxia signaling and cytoskeletal reorganization. Other signalings involved in this process are epithelial to mesenchymal transition (EMT) and epidermal growth factor receptor (EGFR) signalings through the regulation of Yes-associated protein (YAP)/PDZ-binding motif (TAZ) expression. In the current study, we investigated the role of miR-33a family as a (i) modulator of YAP/TAZ expression and (ii) a regulator of EGFR signaling during osteoblast commitments. Starting from the observation on hMSCs and primary osteoblast cell lines (Nh-Ost) in which EMT genes and miR-33a displayed a specific expression, we performed a gain and loss of function study with miR-33a-5p and 3p on hMSCs cells and Nh-Ost. After 24 h of transfections, we evaluated the modulation of EMT and osteoblast genes expression by qRT-PCR, Western blot, and Osteoimage assays. Through bioinformatic analysis, we identified YAP as the putative target of miR-33a-3p. Its role was investigated by gain and loss of function studies with miR-33a-3p on hMSCs; qRT-PCR and Western blot analyses were also carried out. Finally, the possible role of EGFR signaling in YAP/TAZ modulation by miR-33a-3p expression was evaluated. Human MSCs were treated with EGF-2 and EGFR inhibitor for different time points, and qRT-PCR and Western blot analyses were performed. The above-mentioned methods revealed a balance between miR-33a-5p and miR-33a-3p expression during hMSCs osteoblast differentiation. The human MSCs phenotype was maintained by miR-33a-5p, while the maintenance of the osteoblast phenotype in the Nh-Ost cell model was permitted by miR-33a-3p expression, which regulated YAP/TAZ through the modulation of EGFR signaling. The inhibition of EGFR blocked the effects of miR-33a-3p on YAP/TAZ modulation, favoring the maintenance of hMSCs in a committed phenotype. A new possible personalized therapeutic approach to bone regeneration was discussed, which might be mediated by customizing delivery of miR-33a in simultaneously targeting EGFR and YAP signaling with combined use of drugs.

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“…It was recently shown that microRNAs (miRNAs) can play a strong role in the regulation of the signal transduction induced by the members of the TGF-β superfamily. MicroRNAs, which possess 18–25 nucleotides, are small noncoding RNA molecules that can inhibit the translation of targeted mRNAs or induce their degradation (for review see [ 255 ]). Both miR-422a and miR-153 inhibit the post transcriptional expression of the gene encoding TGF-β2 in osteosarcoma cells [ 256 , 257 , 258 ].…”

Section: The Tgf-β Superfamilymentioning

confidence: 99%

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

Jann

Gascon

Roux

et al. 2020

IJMS

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The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors—in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins—not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-β superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-β superfamily and their associated complications are debated.

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Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis

Cited by 88 publications

References 173 publications

Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR‐29a‐3p

Circular RNA circFOXO3 promotes prostate cancer progression through sponging miR‐29a‐3p

MiR-33a Controls hMSCS Osteoblast Commitment Modulating the Yap/Taz Expression Through EGFR Signaling Regulation

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions

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