scholarly journals Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles

Author(s):  
Haigang Cao ◽  
Jieming Liu ◽  
Tianning Du ◽  
Yihao Liu ◽  
Xiaoyu Zhang ◽  
...  

AbstractThe type of myofiber is related to the quality of meat. The slow oxidized myofiber helps to increase the tenderness and juiciness of muscle. Numerous studies have shown that circRNA plays a key role in skeletal muscle development. However, the role of circRNA in porcine skeletal myofiber types is unclear. In this study, we performed high-throughput RNA sequencing to study the differential expression of circRNA in the longissimus dorsi and the soleus muscle. A total of 40,757 circRNAs were identified, of which 181 were significantly different. Interestingly, some circRNAs were involved in metabolism pathways, AMPK, FoxO, and PI3K-Akt signaling pathways. Besides, we focused on a novel circRNA-circMYLK4. By injecting circMYLK4-AAV into piglets, we found that circMYLK4 significantly increased the mRNA and protein levels of the slow muscle marker genes. In summary, our study laid an essential foundation for further research of circRNA in myofiber type conversion and higher meat quality.

2020 ◽  
Author(s):  
Haigang Cao ◽  
Jieming Liu ◽  
Tianning Du ◽  
Yihao Liu ◽  
Xiaoyu Zhang ◽  
...  

Abstract Background: The myofiber type is related to the quality of meat; specifically, slow-oxidized myofiber helps to increase the tenderness and juiciness of meat. An increasing number of studies have shown that circRNAs play a key role in skeletal muscle development. However, the key circRNAs that regulate myofiber types and their roles are still poorly understood.Results: A total of 40757 circRNAs were identified from the longissimus dorsi (LD) and the soleus (Sol) muscles, of which 10388 were co-expressed in the two muscles. Further analysis found 181 differentially expressed circRNAs in the LD compared with Sol. Functional enrichment analysis showed that target genes of differentially expressed circRNA-sponge miRNAs were enriched in the AMPK, FoxO and PI3K-Akt signaling pathways. In addition, we focused on a novel circRNA—circMYLK4. CircMYLK4 significantly increased the mRNA and protein levels of slow muscle marker genes and caused the flesh to turn red.Conclusion: Our study laid an essential foundation for further research on circRNAs in myofiber type conversion and the achievement of higher meat quality.


2020 ◽  
Author(s):  
Haigang Cao ◽  
Jieming Liu ◽  
Tianning Du ◽  
Yihao Liu ◽  
Xiaoyu Zhang ◽  
...  

Abstract Background: The myofiber type is related to the quality of meat; specifically, slow-oxidized myofiber helps to increase the tenderness and juiciness of meat. An increasing number of studies have shown that circRNAs play a key role in skeletal muscle development. However, the key circRNAs that regulate myofiber types and their roles are still poorly understood.Results: A total of 40757 circRNAs were identified from the longissimus dorsi (LD) and the soleus (Sol) muscles, of which 10388 were co-expressed in the two muscles. Further analysis found 181 differentially expressed circRNAs in the LD compared with Sol. Functional enrichment analysis showed that target genes of differentially expressed circRNA-sponge miRNAs were enriched in the AMPK, FoxO and PI3K-Akt signaling pathways. In addition, we focused on a novel circRNA—circMYLK4. CircMYLK4 significantly increased the mRNA and protein levels of slow muscle marker genes and caused the flesh to turn red.Conclusion: Our study laid an essential foundation for further research on circRNAs in myofiber type conversion and the achievement of higher meat quality.


BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yinghui Ling ◽  
Qi Zheng ◽  
Lu Zhu ◽  
Lina Xu ◽  
Menghua Sui ◽  
...  

2014 ◽  
Vol 10 (9) ◽  
pp. 983-989 ◽  
Author(s):  
Wangjun Wu ◽  
Ruihua Huang ◽  
Qinghua Wu ◽  
Pinghua Li ◽  
Jie Chen ◽  
...  

Author(s):  
Qi Wang ◽  
Lin Xu ◽  
Jiro Miura ◽  
Mithun Kumar Saha ◽  
Yume Uemura ◽  
...  

The first and second branchiomeric (branchial arch) muscles are craniofacial muscles that derive from branchial arch mesoderm. In mammals, this set of muscles is indispensable for jaw movement and facial expression. Defects during embryonic development that result in congenital partial absence of these muscles can have significant impact on patients’ quality of life. However, the detailed molecular and cellular mechanisms that regulate branchiomeric muscle development remains poorly understood. Herein we investigated the role of retinoic acid (RA) signaling in developing branchiomeric muscles using mice as a model. We administered all-trans RA (25 mg/kg body weight) to Institute of Cancer Research (ICR) pregnant mice by gastric intubation from E8.5 to E10.5. In their embryos at E13.5, we found that muscles derived from the first branchial arch (temporalis, masseter) and second branchial arch (frontalis, orbicularis oculi) were severely affected or undetectable, while other craniofacial muscles were hypoplastic. We detected elevated cell death in the branchial arch mesoderm cells in RA-treated embryos, suggesting that excessive RA signaling reduces the survival of precursor cells of branchiomeric muscles, resulting in the development of hypoplastic craniofacial muscles. In order to uncover the signaling pathway(s) underlying this etiology, we focused on Pitx2, Tbx1, and MyoD1, which are critical for cranial muscle development. Noticeably reduced expression of all these genes was detected in the first and second branchial arch of RA-treated embryos. Moreover, elevated RA signaling resulted in a reduction in Dlx5 and Dlx6 expression in cranial neural crest cells (CNCCs), which disturbed their interactions with branchiomeric mesoderm cells. Altogether, we discovered that embryonic craniofacial muscle defects caused by excessive RA signaling were associated with the downregulation of Pitx2, Tbx1, MyoD1, and Dlx5/6, and reduced survival of cranial myogenic precursor cells.


2021 ◽  
Author(s):  
Jiansheng Xie ◽  
Hui Wang ◽  
Caiqun Luo ◽  
Xiaoxia Wu ◽  
Jianming Zhang ◽  
...  

Abstract Background: Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction fetuses, but their role and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis in the human extravillous trophoblast HTR-8 cells.Methods: circRNA and miRNA levels were examined using quantitative real-time PCR (RT-PCR). Overexpression plasmid constructs and siRNA were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assay and flow cytometry analysis were performed to evaluate the effect of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed using western blot. Dual luciferase activity assay and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343.Results: Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues as compared to healthy placental control tissues. Hsa_circ_0081343 overexpression possibly inhibits apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviates the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p. Conclusions: Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis. Thus, hsa_circ_0081343 plays a key role in the etiology and pathogenesis of FGR implicating its importance as a novel candidate for targeted FGR therapy.


Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3468
Author(s):  
Anqi Li ◽  
Xiaotong Su ◽  
Yuan Tian ◽  
Guibing Song ◽  
Linsen Zan ◽  
...  

Actin Alpha Cardiac Muscle 1 (ACTC1) gene is a differentially expressed gene screened through the co-culture system of myoblasts-preadipocytes. In order to study the role of this gene in the process of proliferation and differentiation of bovine myoblasts and preadipocytes, the methods of the knockdown, overexpression, and ectopic expression of ACTC1 were used in this study. After ACTC1 knockdown in bovine myoblasts and inducing differentiation, the sizes and numbers of myotube formation were significantly reduced compared to the control group, and myogenic marker genes—MYOD1, MYOG, MYH3, MRF4, MYF5, CKM and MEF2A—were significantly decreased (p < 0.05, p < 0.01) at both the mRNA and protein levels of myoblasts at different differentiation stages (D0, D2, D4, D6 and D8). Conversely, ACTC1 overexpression induced the inverse result. After ectopic expression of ACTC1 in bovine preadipocytes and induced differentiation, the number and size of lipid droplets were significantly higher than those of the control group, and the expression of adipogenic marker genes—FABP4, SCD1, PPARγ and FASN—were significantly increased (p < 0.05, p < 0.01) at the mRNA and protein levels of preadipocytes at different differentiation stages. Flow cytometry results showed that both the knockdown and overexpression of ACTC1 inhibited the normal cell cycle of myoblasts; however, ectopic expression of ACTC1 in adipocytes induced no significant cell cycle changes. This study is the first to explore the role of ACTC1 in bovine myogenesis and lipogenesis and demonstrates that ACTC1 promotes the differentiation of bovine myoblasts and preadipocytes, affecting the proliferation of myoblasts.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ralph Klose ◽  
Alexander Prinz ◽  
Fabian Tetzlaff ◽  
Eva-Maria Weis ◽  
Iris Moll ◽  
...  

AbstractVascular smooth muscle cell (VSMC) dysfunction is a hallmark of small vessel disease, a common cause of stroke and dementia. Two of the most frequently mutated genes in familial small vessel disease are HTRA1 and NOTCH3. The protease HTRA1 cleaves the NOTCH3 ligand JAG1 implying a mechanistic link between HTRA1 and Notch signaling. Here we report that HTRA1 is essential for VSMC differentiation into the contractile phenotype. Mechanistically, loss of HTRA1 increased JAG1 protein levels and NOTCH3 signaling activity in VSMC. In addition, the loss of HTRA1 enhanced TGFβ-SMAD2/3 signaling activity. Activation of either NOTCH3 or TGFβ signaling resulted in increased transcription of the HES and HEY transcriptional repressors and promoted the contractile VSMC phenotype. However, their combined over-activation led to an additive accumulation of HES and HEY proteins, which repressed the expression of contractile VSMC marker genes. As a result, VSMC adopted an immature phenotype with impaired arterial vasoconstriction in Htra1-deficient mice. These data demonstrate an essential role of HTRA1 in vascular maturation and homeostasis by controlling Notch and TGFβ signaling.


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