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

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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Accentuating CircRNA-miRNA-Transcription Factors Axis: A Conundrum in Cancer Research

Frontiers in Pharmacology ◽

10.3389/fphar.2021.784801 ◽

2022 ◽

Vol 12 ◽

Author(s):

Deepti Singh ◽

Prashant Kesharwani ◽

Nabil A. Alhakamy ◽

Hifzur R. Siddique

Keyword(s):

Transcription Factors ◽

Expression Patterns ◽

Regulatory Function ◽

Circular Rnas ◽

Cancer Management ◽

Disease Biology ◽

Scientific World ◽

Cancer Types ◽

Non Coding Rnas ◽

Mirna Sponges

Circular RNAs (circRNAs) are the newly uncovered class of non-coding RNAs being cognized as profound regulators of gene expression in developmental and disease biology. These are the covalently closed RNAs synthesized when the pre-mRNA transcripts undergo a back-splicing event. In recent years, circRNAs are gaining special attention in the scientific world and are no longer considered as “splicing noise” but rather structurally stable molecules having multiple biological functions including acting as miRNA sponges, protein decoys/scaffolds, and regulators of transcription and translation. Further, emerging evidence suggests that circRNAs are also differentially expressed in multiple cancers where they play oncogenic roles. In addition, circRNAs in association with miRNAs change the expression patterns of multiple transcription factors (TFs), which play important roles in cancer. Thus, the circRNA-miRNA-TFs axis is implicated in the progression or suppression of various cancer types and plays a role in cell proliferation, invasion, and metastasis. In this review article, we provide an outline of the biogenesis, localization, and functions of circRNAs specifically in cancer. Also, we highlight the regulatory function of the circRNA-miRNA-TFs axis in the progression or suppression of cancer and the targeting of this axis as a potential therapeutic approach for cancer management. We anticipate that our review will contribute to expanding the knowledge of the research community about this recent and rapidly growing field of circRNAs for further thorough investigation which will surely help in the management of deadly disease cancer.

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The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-β pathway

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01847-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanfeng Gao ◽

Ye Liu ◽

Yuan Fu ◽

Qianhui Wang ◽

Zheng Liu ◽

...

Keyword(s):

Cardiac Fibrosis ◽

Expression Patterns ◽

In Silico Analysis ◽

Significant Negative Correlation ◽

Circular Rnas ◽

Tgf Beta ◽

Rt Pcr ◽

Derivation Cohort ◽

Tgf Β1

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = − 0.797, p < 0.001). Conclusion CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

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Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis

Molecular Cancer ◽

10.1186/s12943-021-01314-w ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Junjie Cen ◽

Yanping Liang ◽

Yong Huang ◽

Yihui Pan ◽

Guannan Shu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Target Genes ◽

Expression Patterns ◽

Luciferase Reporter ◽

Circular Rnas ◽

Proliferation And Metastasis

Abstract Background There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. Method Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. Results Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. Conclusion Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.

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Oligodendroglial Energy Metabolism and (re)Myelination

Life ◽

10.3390/life11030238 ◽

2021 ◽

Vol 11 (3) ◽

pp. 238

Author(s):

Vanja Tepavčević

Keyword(s):

Energy Metabolism ◽

Alternative Energy ◽

Energy Homeostasis ◽

Energy Deficit ◽

Maturation Stage ◽

Trophic Support ◽

Important Contributor ◽

Alternative Energy Sources ◽

Axonal Pathology ◽

Sufficient Energy

Central nervous system (CNS) myelin has a crucial role in accelerating the propagation of action potentials and providing trophic support to the axons. Defective myelination and lack of myelin regeneration following demyelination can both lead to axonal pathology and neurodegeneration. Energy deficit has been evoked as an important contributor to various CNS disorders, including multiple sclerosis (MS). Thus, dysregulation of energy homeostasis in oligodendroglia may be an important contributor to myelin dysfunction and lack of repair observed in the disease. This article will focus on energy metabolism pathways in oligodendroglial cells and highlight differences dependent on the maturation stage of the cell. In addition, it will emphasize that the use of alternative energy sources by oligodendroglia may be required to save glucose for functions that cannot be fulfilled by other metabolites, thus ensuring sufficient energy input for both myelin synthesis and trophic support to the axons. Finally, it will point out that neuropathological findings in a subtype of MS lesions likely reflect defective oligodendroglial energy homeostasis in the disease.

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Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory

Nature Communications ◽

10.1038/s41467-020-18355-2 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 6

Author(s):

Lasse S. Kristensen ◽

Karoline K. Ebbesen ◽

Martin Sokol ◽

Theresa Jakobsen ◽

Ulrik Korsgaard ◽

...

Keyword(s):

Cancer Research ◽

Stromal Cells ◽

Stromal Cell ◽

Expression Patterns ◽

Research Field ◽

Circular Rnas ◽

Spatially Resolved ◽

Cellular Expression ◽

Competitive Endogenous Rnas ◽

Microrna Sponge

Abstract Circular RNAs (circRNAs) have recently gained substantial attention in the cancer research field where most, including the putative oncogene ciRS-7 (CDR1as), have been proposed to function as competitive endogenous RNAs (ceRNAs) by sponging specific microRNAs. Here, we report the first spatially resolved cellular expression patterns of ciRS-7 in colon cancer and show that ciRS-7 is completely absent in the cancer cells, but highly expressed in stromal cells within the tumor microenvironment. Additionally, our data suggest that this generally apply to classical oncogene-driven adenocarcinomas, but not to other cancers, including malignant melanoma. Moreover, we find that correlations between circRNA and mRNA expression, which are commonly interpreted as evidence of a ceRNA function, can be explained by different cancer-to-stromal cell ratios among the studied tumor specimens. Together, these results have wide implications for future circRNA studies and highlight the importance of spatially resolving expression patterns of circRNAs proposed to function as ceRNAs.

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Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

BMC Genomics ◽

10.1186/s12864-021-07786-w ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xiangchun Pan ◽

Wentao Gong ◽

Yingting He ◽

Nian Li ◽

Hao Zhang ◽

...

Keyword(s):

Alternative Splicing ◽

Signaling Pathway ◽

Gene Networks ◽

Profile Analysis ◽

Mirna Gene ◽

Mapk Signaling ◽

Circular Rnas ◽

Ras Signaling ◽

Female Reproduction ◽

Non Coding Rna

Abstract Background In mammals, the ovary is the essential system of female reproduction for the onset of puberty, and the abnormal puberty has negative outcomes on health. CircRNA is a non-coding RNA produced by non-canonical alternative splicing (AS). Several studies have reported that circRNA is involved in the gene regulation and plays an important role in some human diseases. However, the contribution of circRNA has received little known within the onset of puberty in ovary. Results Here, the profiles of ovarian circRNAs across pre-, in- and post-pubertal stages were established by RNA-sEq. In total, 972 circRNAs were identified, including 631 stage-specific circRNAs and 8 tissue-specific circRNAs. The biological functions of parental genes of circRNAs were enriched in steroid biosynthesis, autophagy-animal, MAPK signaling pathway, progesterone-mediated oocyte maturation and ras signaling pathway. Moreover, 5 circRNAs derived from 4 puberty-related genes (ESR1, JAK2, NF1 and ARNT) were found in this study. The A3SS events were the most alternative splicing, but IR events were likely to be arose in post-pubertal ovaries. Besides, the circRNA-miRNA-gene networks were explored for 10 differentially expressed circRNAs. Furthermore, the head-to-tail exon as well as the expressions of 10 circRNAs were validated by the divergent RT-qPCR and sanger sequencing. Conclusions In summary, the profiles of ovarian circRNAs were provided during pubertal transition in gilts, and these results provided useful information for the investigation on the onset of puberty at the ovarian-circRNAs-level in mammals.

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Importance of Adult Dmbx1 in Long-Lasting Orexigenic Effect of Agouti-Related Peptide

Endocrinology ◽

10.1210/en.2015-1560 ◽

2016 ◽

Vol 157 (1) ◽

pp. 245-257 ◽

Cited By ~ 1

Author(s):

Seiichiro Hirono ◽

Eun Young Lee ◽

Shunsuke Kuribayashi ◽

Takahiro Fukuda ◽

Naokatsu Saeki ◽

...

Keyword(s):

Mouse Strain ◽

Energy Homeostasis ◽

Expression Patterns ◽

Critical Role ◽

Fetal Brain ◽

Cre Recombinase ◽

Calcitonin Gene Related Peptide ◽

Adult Brain ◽

Related Peptide ◽

Calcitonin Gene

Abstract Dmbx1 is a brain-specific homeodomain transcription factor expressed primarily during embryogenesis, and its systemic disruption (Dmbx1−/−) in the ICR mouse strain resulted in leanness associated with impaired long-lasting orexigenic effect of agouti-related peptide (AgRP). Because spatial and temporal expression patterns of Dmbx1 change dramatically during embryogenesis, it remains unknown when and where Dmbx1 plays a critical role in energy homeostasis. In the present study, the physiological roles of Dmbx1 were examined by its conditional disruption (Dmbx1loxP/loxP) in the C57BL/6 mouse strain. Although Dmbx1 disruption in fetal brain resulted in neonatal lethality, its disruption by synapsin promoter-driven Cre recombinase, which eliminated Dmbx1 expression postnatally, exempted the mice (Syn-Cre;Dmbx1loxP/loxP mice) from lethality. Syn-Cre;Dmbx1loxP/loxP mice show mild leanness and impaired long-lasting orexigenic action of AgRP, demonstrating the physiological relevance of Dmbx1 in the adult. Visualization of Dmbx1-expressing neurons in adult brain using the mice harboring tamoxifen-inducible Cre recombinase in the Dmbx1 locus (Dmbx1CreERT2/+ mice) revealed Dmbx1 expression in small numbers of neurons in restricted regions, including the lateral parabrachial nucleus (LPB). Notably, c-Fos expression in LPB was increased at 48 hours after AgRP administration in Dmbx1loxP/loxP mice but not in Syn-Cre;Dmbx1loxP/loxP mice. These c-Fos-positive neurons in LPB did not coincide with neurons expressing Dmbx1 or melanocortin 4 receptor but did coincide with those expressing calcitonin gene-related peptide. Accordingly, Dmbx1 in the adult LPB is required for the long-lasting orexigenic effect of AgRP via the neural circuitry involving calcitonin gene-related peptide neurons.

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Enhancer Trapping and Annotation in Zebrafish Mediated with Sleeping Beauty, piggyBac and Tol2 Transposons

Genes ◽

10.3390/genes9120630 ◽

2018 ◽

Vol 9 (12) ◽

pp. 630 ◽

Cited By ~ 1

Author(s):

Dan Shen ◽

Songlei Xue ◽

Shuheng Chan ◽

Yatong Sang ◽

Saisai Wang ◽

...

Keyword(s):

Expression Profiles ◽

Expression Patterns ◽

Genomic Analysis ◽

Sleeping Beauty ◽

Comparative Genomic Analysis ◽

Regulatory Function ◽

Comparative Genomic ◽

Gfp Expression ◽

Enhancer Trapping ◽

Multiple Expression

Although transposon-mediated enhancer trapping (ET) is successfully applied in diverse models, the efficiency of various transposon systems varies significantly, and little information is available regarding efficiency of enhancer trapping by various transposons in zebrafish. Most potential enhancers (Ens) still lack evidence of actual En activity. Here, we compared the differences in ET efficiency between sleeping beauty (SB), piggyBac (PB) and Tol2 transposons. Tol2 represented the highest germline transfer efficiencies at 55.56% (NF0 = 165), followed by SB (38.36%, NF0 = 151) and PB (32.65%, NF0 = 149). ET lines generated by the Tol2 transposon tended to produce offspring with a single expression pattern per line, while PB and SB tended to generate embryos with multiple expression patterns. In our tests, 10 putative Ens (En1–10) were identified by splinkerette PCR and comparative genomic analysis. Combining the GFP expression profiles and mRNA expression patterns revealed that En1 and En2 may be involved in regulation of the expression of dlx1a and dlx2a, while En6 may be involved in regulation of the expression of line TK4 transgene and rps26, and En7 may be involved in the regulation of the expression of wnt1 and wnt10b. Most identified Ens were found to be transcribed in zebrafish embryos, and their regulatory function may involve eRNAs.

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Altered expression patterns of circular RNAs between implantation sites and interimplantation sites in early pregnant mice

Journal of Cellular Physiology ◽

10.1002/jcp.27675 ◽

2018 ◽

Vol 234 (6) ◽

pp. 9862-9872 ◽

Cited By ~ 2

Author(s):

Shuang Zhang ◽

Yubin Ding ◽

Junlin He ◽

Juanjuan Zhang ◽

Xueqing Liu ◽

...

Keyword(s):

Expression Patterns ◽

Circular Rnas ◽

Altered Expression ◽

Pregnant Mice ◽

Implantation Sites

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Current Understanding of Circular RNAs in Systemic Lupus Erythematosus

Frontiers in Immunology ◽

10.3389/fimmu.2021.628872 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongjiang Liu ◽

Yundong Zou ◽

Chen Chen ◽

Yundi Tang ◽

Jianping Guo

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Rna Binding ◽

Rna Binding Proteins ◽

Protein Complexes ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Current Understanding ◽

Circular Rnas ◽

Systemic Lupus

Systemic lupus erythematosus (SLE) is a common and potentially fatal autoimmune disease that affects multiple organs. To date, its etiology and pathogenesis remains elusive. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs with covalently closed loop structure. Growing evidence has demonstrated that circRNAs may play an essential role in regulation of gene expression and transcription by acting as microRNA (miRNA) sponges, impacting cell survival and proliferation by interacting with RNA binding proteins (RBPs), and strengthening mRNA stability by forming RNA-protein complexes duplex structures. The expression patterns of circRNAs exhibit tissue-specific and pathogenesis-related manner. CircRNAs have implicated in the development of multiple autoimmune diseases, including SLE. In this review, we summarize the characteristics, biogenesis, and potential functions of circRNAs, its impact on immune responses and highlight current understanding of circRNAs in the pathogenesis of SLE.

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