Corticosterone-mediated regulation and functions of miR-218-5p in rat brain

AbstractChronic stress is one of the key precipitating factors in major depressive disorder (MDD). Stress associated studies have underscored the mechanistic role of epigenetic master players like microRNAs (miRNAs) in depression pathophysiology at both preclinical and clinical levels. Previously, we had reported changes in miR-218-5p expression in response to corticosterone (CORT) induced chronic stress. MiR-218-5p was one of the most significantly induced miRNAs in the prefrontal cortex (PFC) of rats under chronic stress. In the present report, we have investigated how chronic CORT exposure mechanistically affected miR-218-5p expression in the rat brain and how miR-218 could trigger molecular changes on its downstream regulatory pathways. Elevated expression of miR-218-5p was found in the PFC of CORT-treated rats. A glucocorticoid receptor (GR) targeted Chromatin-Immunoprecipitation (ChIP) assay revealed high GR occupancy on the promoter region of Slit3 gene hosting miR-218-2 in its 3rd intron. RNA-sequencing data based on RNA Induced silencing Complex Immunoprecipitation (RISC-IP) with AGO2 in SH-SY5Y cells detected six consistent target genes of miR-218-5p (APOL4, DTWD1, BNIP1, METTL22, SNAPC1, and HDAC6). The expression of all five genes, except APOL4, was successfully validated with qPCR in CORT-treated rat PFC. Further, Hdac6-based ChIP-seq experiment helped in mapping major genomic loci enriched for intergenic regions in the PFC of CORT-treated rat. A proximity-based gene ontology (GO) analysis revealed a majority of the intergenic sites to be part of key genes implicated in central nervous system functions, notably synapse organization, neuron projection morphogenesis, and axonogenesis. Our results suggest that the upregulation of miR-218-5p in PFC of CORT-treated rats possibly resulted from GR biding in the promoter region of Slit3 gene. Interestingly, Hdac6 was one of the consistent target genes potentially found to regulate CNS related genes by chromatin modification. Collectively, these findings establish the role of miR-218-5p in chronic stress and the epigenetic function it plays to induce chromatin-based transcriptional changes of several CNS genes in triggering stress-induced disorders, including depression. This also opens up the scope to understand the role of miR-218-5p as a potential target for noncoding RNA therapeutics in clinical depression.

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The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

Bioscience Reports ◽

10.1042/bsr20180453 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 33

Author(s):

Qianyun Feng ◽

Sheng Zheng ◽

Jia Zheng

Keyword(s):

Bone Remodeling ◽

Noncoding Rna ◽

Target Genes ◽

Epigenetic Modification ◽

Therapeutic Implications ◽

Small Noncoding Rna ◽

Genetic And Environmental Factors ◽

Underlying Mechanisms ◽

Post Transcriptional Regulation

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

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Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

10.21203/rs.3.rs-18941/v5 ◽

2020 ◽

Author(s):

Fuhui Han ◽

Jing Li ◽

Ranran Zhao ◽

Lirong Liu ◽

Lanlan Li ◽

...

Keyword(s):

Target Genes ◽

Structural Characteristics ◽

Intramuscular Fat ◽

Differentially Expressed ◽

Lipid Deposition ◽

Sequencing Data ◽

Dual Purpose ◽

Intramuscular Lipid ◽

Non Coding Rnas

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China's most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results: We identified a total of 26,247 genes and 6,935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR.Conclusions: Our study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.

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Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

10.21203/rs.3.rs-18941/v4 ◽

2020 ◽

Author(s):

Fuhui Han ◽

Jing Li ◽

Nan Liu ◽

Ranran Zhao ◽

Lirong Liu ◽

...

Keyword(s):

Target Genes ◽

Structural Characteristics ◽

Intramuscular Fat ◽

Differentially Expressed ◽

Lipid Deposition ◽

Sequencing Data ◽

Dual Purpose ◽

Intramuscular Lipid ◽

Non Coding Rnas

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Identification of a novel enhancer of CEBPE essential for granulocytic differentiation

Blood ◽

10.1182/blood.2018886077 ◽

2019 ◽

Vol 133 (23) ◽

pp. 2507-2517 ◽

Cited By ~ 5

Author(s):

Pavithra Shyamsunder ◽

Mahalakshmi Shanmugasundaram ◽

Anand Mayakonda ◽

Pushkar Dakle ◽

Weoi Woon Teoh ◽

...

Keyword(s):

Target Genes ◽

Core Promoter ◽

Transcriptional Start Site ◽

Open Chromatin ◽

Sequencing Data ◽

Granulocytic Differentiation ◽

Circular Chromosome ◽

Chromosome Conformation ◽

Guide Rna

Abstract CCAAT/enhancer binding protein ε (CEBPE) is an essential transcription factor for granulocytic differentiation. Mutations of CEBPE occur in individuals with neutrophil-specific granule deficiency (SGD), which is characterized by defects in neutrophil maturation. Cebpe-knockout mice also exhibit defects in terminal differentiation of granulocytes, a phenotype reminiscent of SGD. Analysis of DNase I hypersensitive sites sequencing data revealed an open chromatin region 6 kb downstream of the transcriptional start site of Cebpe in murine myeloid cells. We identified an interaction between this +6-kb region and the core promoter of Cebpe using circular chromosome conformation capture sequencing (4C-seq). To understand the role of this putative enhancer in transcriptional regulation of Cebpe, we targeted it using catalytically inactive Cas9 fused to Krüppel-associated box (KRAB) domain and observed a significant downregulation of transcript and protein levels of CEBPE in cells expressing guide RNA targeting the +6-kb region. To further investigate the role of this novel enhancer further in myelopoiesis, we generated mice with deletion of this region using CRISPR/Cas9 technology. Germline deletion of the +6-kb enhancer resulted in reduced levels of CEBPE and its target genes and caused a severe block in granulocytic differentiation. We also identified binding of CEBPA and CEBPE to the +6-kb enhancer, which suggests their role in regulating the expression of Cebpe. In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe and required for normal granulocytic differentiation.

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The Evolving Role of MicroRNAs in Endothelial Cell Dysfunction in Response to Infection

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0037-1612623 ◽

2018 ◽

Vol 44 (03) ◽

pp. 216-223 ◽

Cited By ~ 2

Author(s):

Rebecca Watkin ◽

Glenn Fitzpatrick ◽

Steve Kerrigan

Keyword(s):

Endothelial Cell ◽

Cardiovascular System ◽

Noncoding Rna ◽

Target Genes ◽

Cell Function ◽

Critical Role ◽

Microbial Infection ◽

Endothelial Cell Function ◽

Rna Molecules

AbstractThe microRNAs are short noncoding RNA molecules responsible for translational repression and silencing of target genes via binding to the mRNA. They are found in all eukaryotic cells and play a critical role in virtually all physiological processes, including within the cardiovascular system where they influence cellular development, differentiation, cardiovascular function, hemostasis, and programmed cell death. Dysregulated microRNA expression is associated with several conditions ranging from cancer and autoimmune disease to infection. Progressively, it has become increasingly clear that microRNAs are important components of the host response to microbes. The cardiovascular system, coupled with cells of the innate immune system, provide the initial interaction and first response to microbial infection, respectively. This review presents the current state of knowledge regarding the role of microRNAs with emphasis on their role in controlling endothelial cell function.

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Transcriptome analysis reveals the long intergenic noncoding RNAs contributed to skeletal muscle differences between Yorkshire and Tibetan pig

Scientific Reports ◽

10.1038/s41598-021-82126-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ziying Huang ◽

Qianqian Li ◽

Mengxun Li ◽

Changchun Li

Keyword(s):

Skeletal Muscle ◽

Noncoding Rna ◽

Muscle Development ◽

Target Genes ◽

Muscle Growth ◽

Skeletal Muscle Development ◽

Tibetan Pig ◽

The Difference ◽

Long Intergenic Noncoding Rna

AbstractThe difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of GO and KEGG analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.

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Identification and co-expression analysis of long noncoding RNAs and mRNAs involved in the deposition of intramuscular fat in Aohan fine-wool sheep

BMC Genomics ◽

10.1186/s12864-021-07385-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Fuhui Han ◽

Jing Li ◽

Ranran Zhao ◽

Lirong Liu ◽

Lanlan Li ◽

...

Keyword(s):

Target Genes ◽

Structural Characteristics ◽

Intramuscular Fat ◽

Differentially Expressed ◽

Lipid Deposition ◽

Sequencing Data ◽

Dual Purpose ◽

Intramuscular Lipid ◽

Non Coding Rnas

Abstract Background Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China’s most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results We identified a total of 26,247 genes and 6935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. One pathway was significantly enriched, namely tight junction. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed a lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4, MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1, MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR. Conclusions Our study identified the differentially expressed mRNAs and lncRNAs during intramuscular lipid deposition in Aohan fine-wool sheep. The work may widen the knowledge about the annotation of the sheep genome and provide a working basis for investigating intramuscular fat deposition in sheep.

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circAkap17b acts as a miR-7 family molecular sponge to regulate FSH secretion in rat pituitary cells

Journal of Molecular Endocrinology ◽

10.1530/jme-20-0036 ◽

2020 ◽

Vol 65 (4) ◽

pp. 135-148

Author(s):

Chang-Jiang Wang ◽

Fei Gao ◽

Yi-Jie Huang ◽

Dong-Xu Han ◽

Yi Zheng ◽

...

Keyword(s):

Noncoding Rna ◽

Molecular Mechanisms ◽

Target Genes ◽

Luciferase Reporter ◽

Circular Rnas ◽

Pituitary Cells ◽

Rat Pituitary ◽

Rna Immunoprecipitation ◽

Rat Pituitary Cells

The pituitary gland functions as a prominent regulator of diverse physiologic processes by secreting multiple hormones. Circular RNAs (circRNAs) are an emerging novel type of endogenous noncoding RNA that have recently been recognized as powerful regulators participating in various biological processes. However, the physiological roles and molecular mechanisms of circRNAs in pituitary remain largely unclear. Herein, we concentrated on expounding the biological function and molecular mechanism of circRNA in rat pituitary. In this study, we identified a novel circRNA in pituitary tissue, circAkap17b, which was pituitary- and stage-specific. Then, we designed circAkap17b siRNA and constructed an overexpression plasmid to evaluate the effect of loss- and gain-of-circAkap17b function on FSH secretion. Interestingly, silencing circAkakp17b significantly inhibited FSH expression and secretion, while overexpression of circAkap17b enhanced FSH expression and secretion. Furthermore, dual luciferase reporter and RNA immunoprecipitation (RIP) assays confirmed that circAkap17b could serve as miR-7 sponge to regulate target genes. Additionally, miR-7b suppressed FSH expression and secretion by directly targeting Fshb through the dual luciferase reporter and RT-qPCR analysis. Additionally, rescue experiments showed that circAkap17b could regulate FSH secretion in pituitary cells through a circAkap17b-miR-7-Fshb axis. Collectively, we demonstrated that circAkap17b could act as a molecular sponge of miR-7 to upregulate expression of the target gene Fshb and facilitate FSH secretion. These findings provide evidence for a novel regulatory role of circRNAs in pituitary.

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The small noncoding RNA sr8384 determines solvent synthesis and cell growth in industrial solventogenic clostridia

10.1101/663880 ◽

2019 ◽

Author(s):

Yunpeng Yang ◽

Nannan Lang ◽

Huan Zhang ◽

Lu Zhang ◽

Changsheng Chai ◽

...

Keyword(s):

Cell Growth ◽

Clostridium Acetobutylicum ◽

Noncoding Rna ◽

Large Scale ◽

Target Genes ◽

Biological Processes ◽

Small Noncoding Rna ◽

Small Noncoding Rnas ◽

Solventogenic Clostridia

ABSTRACTSmall noncoding RNAs (sncRNAs) are crucial regulatory molecules in organisms and are well known not only for their roles in the control of diverse essential biological processes but also for their value in genetic modification. However, to date, in gram-positive anaerobic solventogenic clostridia (which are a group of important industrial bacteria with exceptional substrate and product diversity), sncRNAs remain minimally explored, leading to a lack of detailed understanding regarding these important molecules and their use as targets for genetic improvement. Here, we performed large-scale phenotypic screens of a transposon-mediated mutant library ofClostridium acetobutylicum, a typical solventogenic clostridial species, and discovered a novel sncRNA (sr8384) that functions as a determinant positive regulator of growth and solvent synthesis. Comparative transcriptomic data combined with genetic and biochemical analyses revealed that sr8384 acts as a pleiotropic regulator and controls multiple targets that are associated with crucial biological processes, through direct or indirect interactions. Notably, modulation of the expression level of either sr8384 or its core target genes significantly increased the growth rate, solvent titer and productivity of the cells, indicating the importance of sr8384-mediated regulatory network inC. acetobutylicum. Furthermore, a homolog of sr8384 was discovered and proven to be functional in another importantClostridiumspecies,C. beijerinckii, suggesting the potential broad role of this sncRNA in clostridia. Our work showcases a previously unknown potent and complex role of sncRNAs in clostridia, providing new opportunities for understanding and engineering these anaerobes, including pathogenicClostridiumspecies.IMPORTANCEThe discovery of sncRNAs as new resources for functional studies and strain modifications are promising strategies in microorganisms. However, these crucial regulatory molecules have hardly been explored in industrially important solventogenic clostridia. Here, we identified sr8384 as a novel determinant sncRNA controlling cellular performance of solventogenicClostridium acetobutylicumand performed detailed functional analysis, which is the most in-depth study of sncRNAs in clostridia to date. We reveal the pleiotropic function of sr8384 and its multiple direct and indirect crucial targets, which represents a valuable source for understanding and optimizing this anaerobe. Of note, manipulation of these targets leads to improved cell growth and solvent synthesis. Our findings provide a new perspective for future studies on regulatory sncRNAs in clostridia.

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Current State and Progress of Research on the Role of lncRNA in HBV-Related Liver Cancer

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.714895 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xueke Wang ◽

Meisong Kang ◽

Chun Liu ◽

Ting Lin ◽

Xiao Han ◽

...

Keyword(s):

Liver Cancer ◽

Tumor Suppressor Genes ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

High Throughput Sequencing ◽

Sequencing Technology ◽

Regulatory Pathways ◽

Current State ◽

B Virus

Hepatocellular carcinoma (HCC) is a malignant tumor with the highest mortality rate in the world, and hepatitis B virus (HBV) plays an important role in its development. Long noncoding RNA (lncRNA) is highly related to the inactivation of tumor suppressor genes and the activation of oncogenes in HCC. Researchers have used high-throughput sequencing technology to identify many noncoding transcripts related to the development of HCC and have studied the interaction between these transcripts and DNA, RNA, or protein to determine the relevant mechanism in the development of HCC. In general, the research on lncRNA represents a new field of cancer research, and the imbalance in lncRNA plays an pivotal role in the occurrence of liver cancer. In this review, we summarize some of the dysfunctional lncRNAs in human HCC associated with HBV infection. Their regulatory pathways, functions, and potential molecular mechanisms in the occurrence and development of HCC are discussed.

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