MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR-206

Koutalianos, Demetris; Koutsoulidou, Andrie; Mastroyiannopoulos, Nikilaos P.; Furling, Denis; Phylactou, Leonidas A.

doi:10.1242/jcs.172288

Cited by 35 publications

(30 citation statements)

References 61 publications

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“…Compared to mocked control cells, si-DNMT3B samples showed of a marked expression of MYOD1, followed by Myogenin and myomiR (miR-133a and miR-206) up-regulation. MYOD1 is a master regulator of myogenesis, since it normally triggers the down-stream molecular events that switch myoblasts from a growing phase to a differentiated state, by directly promoting the expression of miR-206 and many other genes involved in myogenesis [45, 46]. RD proliferating cells show low levels of MYOD1, and increased abundance of this transcription factor has been demonstrated to fully execute the terminal myogenic program [47], this confirming that a controlled amount of MRFs is a fundamental condition for proper skeletal muscle differentiation in ERMS cells.…”

Section: Discussionmentioning

confidence: 99%

DNMT3Bin vitroknocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

et al. 2016

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Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS.

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Section: Discussionmentioning

confidence: 99%

DNMT3Bin vitroknocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

et al. 2016

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“…MiRNAs are crucial players in many pathophysiological processes owing to their promising potential of being novel diagnostic and predictive markers for therapies. Previous studies demonstrated that several miRs can stimulates the expression of Twist [ 34 - 36 ]. In this study, Twist is identified as a new direct target of miR-497.…”

Section: Discussionmentioning

confidence: 99%

Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis

et al. 2016

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Angiogenesis is a critical step in the growth and dissemination of malignant diseases, including pancreatic cancer. Twist has been shown to stimulate angiogenesis in the tumor site. However, whether Twist contributes to angiogenesis in pancreatic cancer remains unknown. In this paper, we found that the expression of Twist was significantly increased in human pancreatic cancer cell lines and pancreatic cancer specimens. It is also closely engaged to adverse clinical feature, diminished survival and angiogenesis in pancreatic cancer patients. The up-regulation of Twist was found to be promoting cell growth, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. By contrast, the silencing of Twist inhibited orthotopic xenograft tumor growth, metastasis and angiogenesis. Subsequent investigations disclosed that Twist was regulated by miR-497 directly, leading to the increased level of Vascular Endothelial Growth Factor-A (VEGFA). Moreover, gain-of-function and loss-of-function studies demonstrated that miR-497 could suppress the pro-proliferative, angiogenic and metastatic ability of pancreatic cancer cells. The ectopic expression of VEGFA obviously abrogated the anti-angiogenic effect induced by Twist knockdown, whereas the silencing of VEGFA markedly rescued the pro-angiogenic effect of Twist. By analyzing the expression levels of miR-497, Twist was found inversely correlated with miR-497 in pancreatic cancer tissues, and a positive correlation was found between Twist and VEGFA levels in pancreatic cancer specimens. In conclusion, our results suggested that the Twist/miR-497/VEGFA axis is significantly correlated with metastasis and angiogenesis in pancreatic cancer.

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“…In addition, other pathways involving miRNAs and the regulation of myogenesis, hypertrophy, or atrophy have been described both in vitro and in vivo . Koutalianos et al ( 53 ) showed that overexpression of MyoD, a myogenic transcription factor, induces the expression of miR-206. In addition, the increase of miR-206 downregulates Twist-1, decreasing the activity of Twist-1, and allowing increased differentiation of muscle cells.…”

Section: Myomirs and Cancer Cachexiamentioning

confidence: 99%

“…The authors reported that muscle cells from patients with myotonic dystrophy type 1 exhibited inhibition of MyoD protein expression and an increase of Twist-1 expression, following a reduction in miR-206 levels. The co-transfection of MyoD and miR-206 regulated the protein content of Twist-1, allowing the differentiation of muscle cells to occur ( 53 ).…”

Section: Myomirs and Cancer Cachexiamentioning

confidence: 99%

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Role of Exosomal MicroRNAs and myomiRs in the Development of Cancer Cachexia-Associated Muscle Wasting

et al. 2018

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Cachexia is a complex metabolic syndrome that promotes great weight loss, with marked muscle mass wasting. In the last years, many efforts have been directed to improve the understanding of the mechanisms involved in the disease. This syndrome is present in up to 80% of cancer patients and, despite its clinical relevance, is underdiagnosed. The orchestration of the molecular and biochemical disruptions observed in cachexia is paralleled by inflammation and the communication among the different body compartments, including the tumor and the skeletal muscle, is still not completely described. One of the mechanisms that may be involved in the transduction of the inflammatory signals and the activation of catabolic status in muscle is the participation of exosomes containing microRNAs (miRNAs) and muscle-specific miRNAs (myomiRs). Exosomes are nanovesicles, measuring from 30 to 100 µm, and able to carry miRNAs in the circulation, promoting cell–cell and tissue–tissue communication in an autocrine, paracrine, and endocrine manner. miRNAs transported in exosomes are preserved from degradation, while these nanoparticles deliver the cargo to specific cell targets, making communication more efficient. Several miRNAs are known to modulate inflammatory pathways, to induce metastasis, to mediate cancer aggressiveness and even to participate in the regulation of protein synthesis and degradation pathways in the skeletal muscle. The aim of this mini-review is to describe the present knowledge about the role of exosomal miRNAs and myomiRs in the induction of muscle mass wasting in cancer cachexia state and to explain which transcription factors, proteins, and pathways are regulated by these molecules.

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MyoD transcription factor induces myogenesis by inhibiting Twist-1 through miR-206

Cited by 35 publications

References 61 publications

DNMT3Bin vitroknocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

DNMT3Bin vitroknocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

Twist promotes angiogenesis in pancreatic cancer by targeting miR-497/VEGFA axis

Role of Exosomal MicroRNAs and myomiRs in the Development of Cancer Cachexia-Associated Muscle Wasting

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