Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis

Liu, Yanjun; Liu, Hongtao; Li, Yang; Mao, Rui; Yang, Huawu; Zhang, Yuanchuan; Zhang, Yu; Guo, Pengsen; Zhan, Dafang; Zhang, Tongtong

doi:10.7150/thno.42417

Cited by 101 publications

(108 citation statements)

References 49 publications

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“…Likewise, Li et al disclosed that CircFUT10 inhibits proliferation and promotes differentiation of cattle myoblast via sponging miR-133a [9]. Additionally, Liu et al found that circular RNA SAMD4A controls adipogenesis through the miR-138-5p/EZH2 Axis in obesity [47]. Therefore, in the present study, we employed miRanda to explore the circRNAs target sites with miRNAs.…”

Section: Discussionmentioning

confidence: 92%

CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation

Zhang

Guo

Pei

et al. 2020

Genes

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The yak (Bos grunniens) is subjected to nutritional deficiency during the whole winter grazing season; deciphering the adipose metabolism and energy homeostasis under cold and nutrients stress conditions could be a novel way to understand the specific mechanism of energy metabolism. Circular RNAs (circRNAs) have elucidated that they play a key role in many biological events, but the regulatory function of adipose development remains mostly unknown. Therefore, the expression pattern of circRNAs were identified for the first time during yak adipocyte differentiation to gain insight into their potential functional involvement in bovine adipogenesis. We detected 7203 circRNA candidates, most of them contained at least two exons, and multiple circRNA isoforms could be generated from one parental gene. Analysis of differential expression circRNAs displayed that 136 circRNAs were differentially expressed at day 12 (Ad) after adipocyte differentiation, compared with the control at day 0 (Pread 0), while 7 circRNAs were detected on day 2. Sanger sequencing validated that six circRNAs had head-to-tail junction, and quantitative real-time PCR (qPCR) results revealed that the expression patterns of ten circRNAs were consistent with their expression levels from RNA-sequencing (RNA-seq) data. We further predicted the networks of circRNA-miRNA-gene based on miRNAs sponging by circRNAs, in which genes were participated in the adipocyte differentiation-related signaling pathways. After that, we constructed several adipocyte differentiation-related ceRNAs and revealed six circRNAs (novel_circ_0009127, novel_circ_0000628, novel_circ_0011513, novel_circ_0010775, novel_circ_0006981 and novel_circ_0001494) were related to adipogenesis. Furthermore, we analyzed the homology among yak, human and mouse circRNAs and found that 3536 yak circRNAs were homologous to human and mouse circRNAs. In conclusion, these findings provide a solid basis for the investigation of yak adipocyte differentiation-related circRNAs and serve as a great reference to study the energy metabolism of high-altitude animals.

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Section: Discussionmentioning

confidence: 92%

CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation

Zhang

Guo

Pei

et al. 2020

Genes

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“…For example, circularRNA SNX29 sponges miR-744 to regulate proliferation and differentiation of myoblasts by activating the Wnt5a/Ca signaling pathway [47]. CircSAMD4A regulates preadipocyte differentiation by acting as a miR-138-5p sponge, and thus increasing EZH2 expression [48]. CircRNA_0046366 inhibits hepatocellular steatosis by abolishing the miR-34a-dependent inhibition of PPARα [49].…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Regulation of Circular RNA Expression During Ningxiang Pig Skeletal Muscle, Subcutaneous Fat, and Liver Development

Li¹,

Gong²,

Zhang³

et al. 2020

Preprint

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Background: In recent years, thousands of different circular RNA (circRNAs) have been discovered by comparative analysis of different pig breeds. However, very few studies have been conducted on the spatiotemporal expression pattern of circRNA during organ development which is crucial for functional and evolutionary analysis.Results: Here, we systematically analyzed circRNAs associated with fatty acid metabolism in the three main organs (muscle, fat and liver) for four growth time points (30d, 90d, 150d and 210d after birth) of Ningxiang pigs, a famous native pig breeds in China, known for its excellent meat quality. We identified 61,683 circRNAs and analyzed their molecular characteristics, potential functions, and interaction with miRNA. The circRNAs showed striking spatiotemporal specificity in the form of dynamic expression. At 90d, the number and complexity of differentially expressed circRNAs in the liver is the most obvious. We used STEM (Short Time Series Expression Miner) to perform time series analysis on differentially expressed circRNAs, and found that there are multiple model spectra that are significantly enriched with time changes in all the three organs. All the significantly changed circRNAs, miRNAs and mRNAs obtained from STEM analysis of each tissue were used to confirm that the circRNA and mRNA have a targeting relationship with miRNA. It is worth noting that we screened out 2384 (fat), 2672 (muscle) and 9187 (liver) circRNAs-miRNA-mRNA network pairs related to developmental time changes. Finally, we used fluorescence in situ hybridization（FISH）to show the dynamic subcellular localization of circRNA during development.Conclusion: To a certain extent, these data indicate that circRNA is highly abundant in muscle, fat and liver, and is dynamically expressed in a spatiotemporal manner. These results suggest that circRNAs play an important role in fat metabolism of Ningxiang pigs. Our findings also provide new ideas and perspectives for the study of Ningxiang pigs' lipid metabolism regulation pathway and meat quality traits.

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“…These transcripts were shown to be implicated in multiple biological processes including lipid metabolic and cell differentiation processes [73]. More recently, an interesting study indicated that circSAMD4A (sterile alpha motif domain containing 4A; also named hsa_circ_0004846) controls adipogenesis in obesity by binding to miR-138-5p [74]. In high-fat diet (HFD)-induced obese mice, mmu_circ_0000529 (the homologous mouse circRNA for circSAMD4A) knockdown reversed the associated weight gain, reduced food intake, lowered body fat, and increased energy expenditure.…”

Section: Circrnas In Adipogenesis and Obesitymentioning

confidence: 99%

“…In high-fat diet (HFD)-induced obese mice, mmu_circ_0000529 (the homologous mouse circRNA for circSAMD4A) knockdown reversed the associated weight gain, reduced food intake, lowered body fat, and increased energy expenditure. It is worth noting that these mice also exhibited increased insulin sensitivity and glucose tolerance [74]. Mechanistically, in vitro experiments showed that circSAMD4A can bind to miR-138-5p and act as a miRNA sponge to subsequently regulate EZH2 expression [74].…”

Section: Circrnas In Adipogenesis and Obesitymentioning

confidence: 99%

The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

Zaiou

2020

Cells

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Circular RNAs (circRNAs) are genome transcripts that are produced from back-splicing of specific regions of pre-mRNA. These single-stranded RNA molecules are widely expressed across diverse phyla and many of them are stable and evolutionary conserved between species. Growing evidence suggests that many circRNAs function as master regulators of gene expression by influencing both transcription and translation processes. Mechanistically, circRNAs are predicted to act as endogenous microRNA (miRNA) sponges, interact with functional RNA-binding proteins (RBPs), and associate with elements of the transcriptional machinery in the nucleus. Evidence is mounting that dysregulation of circRNAs is closely related to the occurrence of a range of diseases including cancer and metabolic diseases. Indeed, there are several reports implicating circRNAs in cardiovascular diseases (CVD), diabetes, hypertension, and atherosclerosis. However, there is very little research addressing the potential role of these RNA transcripts in the occurrence and development of obesity. Emerging data from in vitro and in vivo studies suggest that circRNAs are novel players in adipogenesis, white adipose browning, obesity, obesity-induced inflammation, and insulin resistance. This study explores the current state of knowledge on circRNAs regulating molecular processes associated with adipogenesis and obesity, highlights some of the challenges encountered while studying circRNAs and suggests some perspectives for future research directions in this exciting field of study.

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Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis

Cited by 101 publications

References 49 publications

CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation

CircRNA Expression Profile during Yak Adipocyte Differentiation and Screen Potential circRNAs for Adipocyte Differentiation

Spatiotemporal Regulation of Circular RNA Expression During Ningxiang Pig Skeletal Muscle, Subcutaneous Fat, and Liver Development

The Emerging Role and Promise of Circular RNAs in Obesity and Related Metabolic Disorders

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