HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles

Ferrari, Luca; Bragato, Cinzia; Brioschi, L.; Spreafico, M.; Esposito, Simona; Pezzotta, Alex; Pizzetti, Fabrizio; Moreno-Fortuny, Artal; Bellipanni, Gianfranco; Giordano, Antonio; Riva, Paola; Frabetti, Flavia; Viani, Paola; Cossu, Giulio; Mora, Marina; Marozzi, Anna; Pistocchi, Anna

doi:10.1002/jcp.27341

Cited by 12 publications

(12 citation statements)

References 52 publications

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“…This led us to consider alternative mechanisms of growth arrest elicited by PCI treatment. Studies show that canonical WNT signaling is activated by HDAC8 (Tian et al, 2015;Ferrari et al, 2019). We now show that canonical Wnt pathway is significantly downregulated both in cell lines and in zebrafish embryos following HDAC8 inhibition.…”

Section: Discussionmentioning

confidence: 54%

“…We wished to identify a mechanism of action responsible for PCI-induced growth arrest in HL60 cells that responded to PCI inhibition without undergoing apoptosis being p53-null. Recently, we and others demonstrated that HDAC8 activates canonical Wnt pathway (Tian et al, 2015;Ferrari et al, 2019), which is frequently dysregulated in AML (Gruszka et al, 2019). We investigated whether Wnt signaling was affected by HDAC8 inhibition in AML cell line.…”

Section: Hdac8 Inhibition Downregulates Canonical Wnt Pathwaymentioning

confidence: 98%

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HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia

Spreafico

Gruszka

Valli

et al. 2020

Front. Cell Dev. Biol.

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Histone deacetylase 8 (HDAC8), a class I HDAC that modifies non-histone proteins such as p53, is highly expressed in different hematological neoplasms including a subtype of acute myeloid leukemia (AML) bearing inversion of chromosome 16 [inv(16)]. To investigate HDAC8 contribution to hematopoietic stem cell maintenance and myeloid leukemic transformation, we generated a zebrafish model with Hdac8 overexpression and observed an increase in hematopoietic stem/progenitor cells, a phenotype that could be reverted using a specific HDAC8 inhibitor, PCI-34051 (PCI). In addition, we demonstrated that AML cell lines respond differently to PCI treatment: HDAC8 inhibition elicits cytotoxic effect with cell cycle arrest followed by apoptosis in THP-1 cells, and cytostatic effect in HL60 cells that lack p53. A combination of cytarabine, a standard anti-AML chemotherapeutic, with PCI resulted in a synergistic effect in all the cell lines tested. We, then, searched for a mechanism behind cell cycle arrest caused by HDAC8 inhibition in the absence of functional p53 and demonstrated an involvement of the canonical WNT signaling in zebrafish and in cell lines. Together, we provide the evidence for the role of HDAC8 in hematopoietic stem cell differentiation in zebrafish and AML cell lines, suggesting HDAC8 inhibition as a therapeutic target in hematological malignancies. Accordingly, we demonstrated the utility of a highly specific HDAC8 inhibition as a therapeutic strategy in combination with standard chemotherapy.

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Section: Discussionmentioning

confidence: 54%

Section: Hdac8 Inhibition Downregulates Canonical Wnt Pathwaymentioning

confidence: 98%

HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia

Spreafico

Gruszka

Valli

et al. 2020

Front. Cell Dev. Biol.

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“…4A). Besides, WNT signaling pathway is involved in the control of satellite cell differentiation and regeneration [73,74], while Hippo signaling pathway is also an essential pathway known to be involved in myogenesis [75,76].…”

Section: Discussionmentioning

confidence: 99%

CDR1as related miRNA-mRNA networks in differentiating goat skeletal muscle satellite cells

Kyei

Liu

et al. 2020

Preprint

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Background: Myogenesis is a complex process controlled by several coding and non-coding RNAs (ncRNAs) such as circular RNAs (circRNAs) that well-known function as endogenous microRNAs (miRNAs) sponges. Over the past few years, numerous circRNAs have been known and their roles in biological processes have begun to be understood. Cerebellar Degeneration-Related protein 1 antisense (CDR1as), the most spotlighted circRNA as miR-7 sponge that has been blooming circRNAs’ research for a decade, and can potentially sponge several miRNAs in disease and muscle physiology. Nevertheless, the linear-RNAs-differed character that the acute interventions for circRNAs do not affect miRNAs levels, and has retarded the transcriptome-wide discovery of miRNAs sponged by. Therefore, the purpose of this study was to provide the transcriptomic effect of CDR1as during muscle differentiation.Methods: siCDR1as and siDICER1 were transfected into goat skeletal muscle satellite cells (SMSCs). RNA-seq technology and bioinformatics tools were used to analyze genes that are deregulated by siCDR1as and siDICER1. quantitative PCR was used to verify the expression levels of the differentially expressed mRNAs and miRNAs. Results: Here, to systematically identify miRNAs targeting CDR1as, we employed the critical enzyme DICER1 that governs the biogenesis of miRNAs. The deficiency of either DICER1 or CDR1as inhibited myogenic differentiation of SMSCs, and knockdown of DICER1 decreased the expression of CDR1as. Moreover, we screened for the targeted messenger RNAs (mRNAs) and miRNAs in SMSCs transfected with siDICER1 or siCDR1as respectively and found out that some well-known muscle-related pathways such as phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, Rap1 signaling pathway, and MAPK signaling pathway were enriched in all groups. Further, regarding the miRNAs identified in siDICER1 and siCDR1as together with the sequence complementary information, we identified 11 miRNAs including miR-1, miR-206, and miR-27a-5p which are more likely to be novel targets for CDR1as. Conclusion: In summary, our study provides a perspective on the potential functions and relationship between CDR1as and DICER1 during muscle development.

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“…The growth and development of the skeletal muscle is affected by a variety of signaling pathways including Wnt (Suzuki et al, ; Ferrari et al, ), Notch (Zhu et al, ), and PI3K. Many studies have shown that PI3K/AKT regulates cell proliferation by modulating the expression of downstream target proteins, such as mTOR, NF‐κB, and P70S6K (Ge et al, ; Li et al, ; Ye, ).…”

Section: Discussionmentioning

confidence: 99%

WDR13 promotes the differentiation of bovine skeletal muscle‐derived satellite cells by affecting PI3K/AKT signaling

Tong

et al. 2019

Cell Biology International

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Muscle satellite cells are usually at rest, and when externally stimulated or regulated, they can be further differentiated by cell fusion to form new myotubes and muscle fibers. WD repeat domain 13 (WDR13) is highly conserved in vertebrates. Studies have shown that mice lacking the Wdr13 gene develop mild obesity, hyperinsulinemia, and increased islet β cell proliferation. However, the role of WDR13 in bovine cells is unclear. Here, we investigated the effect of WDR13 on bovine skeletal muscle‐derived satellite cells (MDSCs). We found that WDR13 was upregulated in bovine MDSCs using western blotting and immunofluorescence experiments. Moreover, activation and inhibition of WDR13 expression increased and decreased cell differentiation, respectively, suggesting that WDR13 promotes bovine MDSC differentiation. To further understand the mechanism of action of WDR13, we examined changes in the PI3K/AKT signaling pathway following WDR13 activation or inhibition. In addition, cells were treated with a phosphoinositide kinase 3 (PI3K) inhibitor, LY294004, to observe cell differentiation. The results showed that activation of WDR13 inhibited the PI3K/AKT signaling pathway and enhanced cell differentiation. These data suggest that WDR13 can promote the differentiation of bovine MDSCs by affecting the PI3K/AKT signaling pathway.

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HDAC8 regulates canonical Wnt pathway to promote differentiation in skeletal muscles

Cited by 12 publications

References 52 publications

HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia

HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia

CDR1as related miRNA-mRNA networks in differentiating goat skeletal muscle satellite cells

WDR13 promotes the differentiation of bovine skeletal muscle‐derived satellite cells by affecting PI3K/AKT signaling

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