MiR-501-3p Forms a Feedback Loop with FOS, MDFI, and MyoD to Regulate C2C12 Myogenesis

Hou, Lianjie; Zhu, Linhui; Huaqin, LI; Jiang, Feng; Cao, Lingbo; Hu, Ching Yuan; Wang, Chong

doi:10.3390/cells8060573

Cited by 16 publications

(11 citation statements)

References 29 publications

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“…The oral administration of at RA to pregnant mice is known to induce CP ( Abbott et al, 1989 ; Ross et al, 2000 ; Wang et al, 2002 ; Lai et al, 2003 ; Yao et al, 2011 ; Havasi et al, 2013 ; Hu et al, 2013 ; Hou et al, 2019 ; Roberts, 2020 ). However, the amount and timing of at RA administration that induces CP may differ in each mouse strain and protocol.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Yoshioka

Mikami

Ramakrishnan

et al. 2021

Front. Cell Dev. Biol.

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Cleft lip with/without cleft palate (CL/P) is one of the most common congenital birth defects, showing the complexity of both genetic and environmental contributions [e.g., maternal exposure to alcohol, cigarette, and retinoic acid (RA)] in humans. Recent studies suggest that epigenetic factors, including microRNAs (miRs), are altered by various environmental factors. In this study, to investigate whether and how miRs are involved in cleft palate (CP) induced by excessive intake of all-trans RA (atRA), we evaluated top 10 candidate miRs, which were selected through our bioinformatic analyses, in mouse embryonic palatal mesenchymal (MEPM) cells as well as in mouse embryos treated with atRA. Among them, overexpression of miR-27a-3p, miR-27b-3p, and miR-124-3p resulted in the significant reduction of cell proliferation in MEPM cells through the downregulation of CP-associated genes. Notably, we found that excessive atRA upregulated the expression of miR-124-3p, but not of miR-27a-3p and miR-27b-3p, in both in vivo and in vitro. Importantly, treatment with a specific inhibitor for miR-124-3p restored decreased cell proliferation through the normalization of target gene expression in atRA-treated MEPM cells and atRA-exposed mouse embryos, resulting in the rescue of CP in mice. Taken together, our results indicate that atRA causes CP through the induction of miR-124-3p in mice.

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Section: Resultsmentioning

confidence: 99%

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Yoshioka

Mikami

Ramakrishnan

et al. 2021

Front. Cell Dev. Biol.

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“…Among them, we found that at RA specifically induced miR-4680-3p expression, which in turn suppressed expression of ERBB2 and JADE1 . While expression of some predicted genes targeted by miR-4680-3p was not changed by miR-4680-3p overexpression in HEPM cells, these genes may be regulated by a combination of other miRs or through feedback loops reported in several cancer cell lines and in C2C12 cells, an immortalized mouse myoblast cell line (Hou et al, 2019 ; Liu et al, 2019 ; Quan et al, 2019 ).…”

Section: Discussionmentioning

confidence: 98%

“…All-trans retinoic acid ( at RA), a derivative of vitamin A, is the most active retinoid that plays important roles in a variety of biological processes, including cell proliferation, differentiation, and extracellular matrix production (Wang and Kirsch, 2002 ; Lai et al, 2003 ; Rhinn and Dolle, 2012 ; Cunningham and Duester, 2015 ). While at RA is widely used in the treatments of skin diseases and cancers (Karsy et al, 2010 ; Siddikuzzaman and Berlin Grace, 2011 ; Mihaly et al, 2012 ), excessive intake of at RA, a known teratogen, disrupts embryogenesis, causing birth defects (Abbott et al, 1989 ; Ross et al, 2000 ; Roberts, 2020 ) including cleft palate (Abbott et al, 1989 ; Ross et al, 2000 ; Wang and Kirsch, 2002 ; Lai et al, 2003 ; Yao et al, 2011 ; Havasi et al, 2013 ; Hu et al, 2013 ; Hou et al, 2019 ; Roberts, 2020 ). Recent studies show that at RA alters the expression of miRs in human cancer cell lines (Liu et al, 2018 , 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Excessive All-Trans Retinoic Acid Inhibits Cell Proliferation Through Upregulated MicroRNA-4680-3p in Cultured Human Palate Cells

Yoshioka

Ramakrishnan

Shim

et al. 2021

Front. Cell Dev. Biol.

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Cleft palate is the second most common congenital birth defect, and both environmental and genetic factors are involved in the etiology of the disease. However, it remains largely unknown how environmental factors affect palate development. Our previous studies show that several microRNAs (miRs) suppress the expression of genes involved in cleft palate. Here we show that miR-4680-3p plays a crucial role in cleft palate pathogenesis. We found that all-trans retinoic acid (atRA) specifically induces miR-4680-3p in cultured human embryonic palatal mesenchymal (HEPM) cells. Overexpression of miR-4680-3p inhibited cell proliferation in a dose-dependent manner through the suppression of expression of ERBB2 and JADE1, which are known cleft palate-related genes. Importantly, a miR-4680-3p-specific inhibitor normalized cell proliferation and altered expression of ERBB2 and JADE1 in cells treated with atRA. Taken together, our results suggest that upregulation of miR-4680-3p induced by atRA may cause cleft palate through suppression of ERBB2 and JADE1. Thus, miRs may be potential targets for the prevention and diagnosis of cleft palate.

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“…c-Fos is a subunit of transcription factor complex activator protein-1 (AP-1) [41], that binds to the MyoD promotor and inhibits MyoD transcription in proliferating myoblasts [42]. Overexpression of c-Fos has been shown to promote proliferation and inhibit differentiation in C2C12 myoblasts [43]. This suggests that increased c-Fos expression after shear-loading may induce MuSC proliferation.…”

Section: Discussionmentioning

confidence: 99%

Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche

Haroon

Klein‐Nulend

Bakker

et al. 2020

Preprint

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Background: Muscle stem cells (MuSCs) are requisite for skeletal muscle regeneration and homeostasis. Proper functioning of MuSCs, including activation, proliferation, and fate decision, is determined by an orchestrated series of events and communication between MuSCs and their niche consisting of the host myofiber and neighbouring cells. A multitude of biochemical stimuli are known to regulate fate and function of MuSCs. However, in addition to biochemical factors, it is conceivable that MuSCs residing between basal lamina and sarcolemma of myofibers are subjected to mechanical forces during muscle stretch-shortening cycles due to myofascial connections between MuSCs and myofibers. MuSCs have been shown to respond to mechanical forces in vitro but it remains to be proven whether physical forces are also exerted on MuSCs in their native niche and whether they contribute to the functioning and fate of MuSCs. Methods: MuSCs deformation in their native niche resulting from mechanical loading of ex vivo myofiber bundles were visualized utilizing mT/mG double-fluorescent Cre-reporter mouse and multiphoton microscopy. MuSCs were subjected to 1 hour pulsating fluid shear stress with a peak shear stress rate of 8.8 Pa/s. After treatment, nitric oxide and mRNA expression levels of genes involved in regulation of MuSC proliferation and differentiation were determined. Results: Ex vivo stretching of extensor digitorum longus and soleus myofiber bundles caused compression as well as tensile and shear deformation of MuSCs in their niche. MuSCs responded to pulsating fluid shear stress in vitro with increased nitric oxide production and an upward trend in iNOS mRNA levels, while nNOS expression was unaltered. Pulsating fluid shear stress enhanced gene expression of c-Fos, Cdk4, and IL-6, while expression of Wnt1, MyoD, Myog, Wnt5a, COX2, Rspo1, Vangl2, Wnt10b, and MGF remained unchanged. Conclusions: We conclude that MuSCs in their native niche are subjected to force-induced deformations due to myofiber stretch-shortening. Moreover, MuSCs are mechanoresponsive as 4 evident by pulsating fluid shear stress-mediated expression of factors by MuSCs known to promote proliferation. BACKGROUND Skeletal muscle regeneration requires activation and proliferation of muscle stem cells (MuSCs). During organismal aging, the number of MuSCs is reduced and MuSCs lose their proliferation potential [1]. Moreover, muscle pathologies characterized by impaired regeneration by MuSCs lead to atrophy and fibrosis [2]. In young, un-injured muscles, myofiber hypertrophy is accompanied by MuSC activation, proliferation, and subsequent fusion with the host myofiber to increase myonuclei numbers [3]. This ensures that the myonuclear domain does not exceed a critical size [3]. Understanding the mechanisms underlying MuSC function is required for adequate strategies to maintain MuSC self-renewal and regenerative function. During regeneration a multitude of growth factors and cytokines are secreted by myofibers, neighboring immune cells, and fibroblasts, whic...

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MiR-501-3p Forms a Feedback Loop with FOS, MDFI, and MyoD to Regulate C2C12 Myogenesis

Cited by 16 publications

References 29 publications

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

MicroRNA-124-3p Plays a Crucial Role in Cleft Palate Induced by Retinoic Acid

Excessive All-Trans Retinoic Acid Inhibits Cell Proliferation Through Upregulated MicroRNA-4680-3p in Cultured Human Palate Cells

Myofiber stretch induces tensile and shear deformation of muscle stem cells in their native niche

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