scholarly journals Transcriptomes Analysis Reveals the Regulatory Roles of Noncoding RNA in Tanshinones Synthesis Pathway of Salvia Miltiorrhiza

2021 ◽  
Author(s):  
Caicai Lin ◽  
Changhao Zhou ◽  
Zhongqian Liu ◽  
Xingfeng Li ◽  
Zhenqiao Song
Keyword(s):  
Noncoding Rna ◽  
Target Genes ◽  
Salvia Miltiorrhiza ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Synthesis Process ◽  
Circular Rnas ◽  
Regulation Mechanism ◽  
Pentatricopeptide Repeat ◽  
Specific Expression

Abstract Background: Long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) have been shown to play fundamental roles in plant development. However, the information of these noncoding RNAs (ncRNAs) in Salvia miltiorrhiza remains largely unexplored. In this study, the expression pattern of ncRNAs in six tissues from the same strain of S. miltiorrhiza was analyzed to study the biological function of ncRNAs on active ingredients synthesis.Methods: Analysis of tanshinone content differences of two root simples was carried out on high-performance liquid chromatography (HPLC). RNA sequencing, GO and KEGG enrichment analysis were applied to analyzing the targets of diferentially expressed ncRNAs in different organs.Results: A total of 6,929 lncRNAs, 6,239 circRNAs, and 360 miRNAs were identified. Forty-eight lncRNAs, 70 miRNAs, and 26 circRNAs expressed differentially between red and white root tissues with significantly different tanshinone content. GO and KEGG pathway analysis of target genes of differently expressed ncRNAs indicated that some target genes are involved in the synthesis pathway of terpene, including diterpene and sesquiterpene. We also found many target genes related to secondary metabolites, including 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate Synthase (SmMCS) and several CYP450s. Furthermore, most target genes may be related to the resistance of pathogens, such as receptor kinases, disease-resistant proteins, and pentatricopeptide repeat-containing proteins. Conclusions: The present study exhibited the tissue-specific expression patterns of ncRNAs preliminarily in S. miltiorrhiza, which may reflect that the formation of white root or red root is related to regulation by ncRNAs. It would provide a basis for further research about the regulation mechanism in the tanshinone synthesis process.

scholarly journals Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao-Yu Guo ◽  
Ming-Ke Guo ◽  
Zhong-Yuan Wan ◽  
Fang Song ◽  
Hai-Qiang Wang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Form Complex ◽  
Underlying Mechanisms

AbstractIntervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

scholarly journals Roles of noncoding RNAs in preeclampsia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ningxia Sun ◽  
Shiting Qin ◽  
Lu Zhang ◽  
Shiguo Liu
Keyword(s):  
Noncoding Rna ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Noncoding Rnas ◽  
Perinatal Period ◽  
Multiple Organ ◽  
Present Review ◽  
Circular Rnas ◽  
Clinical Value ◽  
Noninvasive Biomarkers

AbstractPreeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the “junk” of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

CircSOD2: A Novel Regulator for Smooth Muscle Proliferation and Neointima Formation

2021 ◽  
Author(s):  
Xiaohan Mei ◽  
Xiao-Bing Cui ◽  
Yiran Li ◽  
Shi-You Chen
Keyword(s):  
Smooth Muscle ◽  
Vascular Injury ◽  
Noncoding Rna ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Circular Rna ◽  
In Vivo Studies ◽  
Circular Rnas ◽  
Neointima Formation ◽  
Specific Expression

Objective: Vascular smooth muscle cell (SMC) proliferation contributes to neointima formation following vascular injury. Circular RNA—a novel type of noncoding RNA with closed-loop structure—exhibits cell- and tissue-specific expression patterns. However, the role of circular RNA in SMC proliferation and neointima formation is largely unknown. The objective of this study is to investigate the role and mechanism of circSOD2 in SMC proliferation and neointima formation. Approach and Results: Circular RNA profiling of human aortic SMCs revealed that PDGF (platelet-derived growth factor)-BB up- and downregulated numerous circular RNAs. Among them, circSOD2, derived from back-splicing event of SOD2 (superoxide dismutase 2), was significantly enriched. Knockdown of circSOD2 by short hairpin RNA blocked PDGF-BB–induced SMC proliferation. Inversely, circSOD2 ectopic expression promoted SMC proliferation. Mechanistically, circSOD2 acted as a sponge for miR-206, leading to upregulation of NOTCH3 and NOTCH3 signaling, which regulates cyclin D1 and CDK (cyclin-dependent kinase) 4/6. In vivo studies showed that circSOD2 was induced in neointima SMCs in balloon-injured rat carotid arteries. Importantly, knockdown of circSOD2 attenuated injury-induced neointima formation along with decreased neointimal SMC proliferation. Conclusions: CircSOD2 is a novel regulator mediating SMC proliferation and neointima formation following vascular injury. Therefore, circSOD2 could be a potential therapeutic target for inhibiting the development of proliferative vascular diseases.

scholarly journals 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

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.

scholarly journals Circular RNAs as Novel Diagnostic Biomarkers and Therapeutic Targets in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Jianwen Yu ◽  
Danli Xie ◽  
Naya Huang ◽  
Qin Zhou
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Circular Rnas ◽  
Specific Expression ◽  
Glomerular Diseases ◽  
Diagnosis And Prognosis

Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have aroused growing attention in this decade. They are widely expressed in eukaryotes and generally have high stability owing to their special closed-loop structure. Many circRNAs are abundant, evolutionarily conserved, and exhibit cell-type-specific and tissue-specific expression patterns. Mounting evidence suggests that circRNAs have regulatory potency for gene expression by acting as microRNA sponges, interacting with proteins, regulating transcription, or directly undergoing translation. Dysregulated expression of circRNAs were found in many pathological conditions and contribute to the pathogenesis and progression of various disorders, including renal diseases. Recent studies have revealed that circRNAs may serve as novel reliable biomarkers for the diagnosis and prognosis prediction of multiple kidney diseases, such as renal cell carcinoma (RCC), acute kidney injury (AKI), diabetic kidney disease (DKD), and other glomerular diseases. Furthermore, circRNAs expressed by intrinsic kidney cells are shown to play a substantial role in kidney injury, mostly reported in DKD and RCC. Herein, we review the biogenesis and biological functions of circRNAs, and summarize their roles as promising biomarkers and therapeutic targets in common kidney diseases.

Abstract 91: Genome-wide Identification and Characterization of Cardiac Hypertrophy-related Long Noncoding RNAs in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Zhanpeng Huang ◽  
Gengze Wu ◽  
Jian-Hua Yang ◽  
Jian Ding ◽  
Jinghai Chen ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Target Genes ◽  
Troponin T ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Functional Screening ◽  
Loss Of Function ◽  
Specific Expression ◽  
Functional Conservation ◽  
Virus Serotype

Long noncoding RNAs (LncRNAs) are RNA transcripts longer than 200 nucleotides that lack protein-coding potential. Although thousands of lncRNAs have been identified, only a few have been linked to cardiac gene expression and function. In this study, we identified, from genome-scale RNA-seq data, 12 candidate lncRNAs associated with cardiac hypertrophy (CH-lncRNAs). The expression of these lncRNAs was altered in mouse models of cardiac hypertrophy induced by transverse aortic constriction (TAC)- or CnA transgene. To determine the function of these lncRNAs, we developed an adeno-associated virus serotype 9 (AAV9)-based functional screening in postnatal mice. An AAV9:cTNT vector, in which the cardiac troponin T (cTNT) promoter was used to direct cardiac-specific expression of target genes, was utilized to overexpress or knockdown candidate lncRNAs in mouse hearts. Postnatal day 1 wild type or CnA transgenic pups were injected with AAV9 viruses and cardiac function was measured one and two months later. Thus far, we have tested 15 candidate lncRNAs for both gain- and loss-of-function studies. Among them, two lncRNAs were demonstrated regulating hypertrophy growth when knocked down. Finally, we identified the human homologues of CH-lncRNA through analyzing the conservation of the promoter regions of lncRNA genes. We showed that the expression of these human CH-lncRNA was dysregulated in human diseased hearts, suggesting the functional conservation of these lncRNAs in cardiac disease. Our study therefore demonstrated that lncRNAs are important regulator of cardiac hypertrophy and disease.

scholarly journals Noncoding RNAs in Vascular Diseases

2020 ◽  
Vol 126 (9) ◽  
pp. 1127-1145 ◽  
Author(s):  
Nicolas Jaé ◽  
Stefanie Dimmeler
Keyword(s):  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Vascular Diseases ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Therapeutic Targeting ◽  
Rna Transcripts ◽  
Sequencing Technologies ◽  
Different Types

The advent of deep sequencing technologies led to the identification of a considerable amount of noncoding RNA transcripts, which are increasingly recognized for their functions in controlling cardiovascular diseases. MicroRNAs have already been studied for a decade, leading to the identification of several vasculoprotective and detrimental species, which might be considered for therapeutic targeting. Other noncoding RNAs such as circular RNAs, YRNAs, or long noncoding RNAs are currently gaining increasing attention, and first studies provide insights into their functions as mediators or antagonists of vascular diseases in vivo. The present review article will provide an overview of the different types of noncoding RNAs controlling the vasculature and focus on the developing field of long noncoding RNAs.

scholarly journals Research Status of Differentially Expressed Noncoding RNAs in Type 2 Diabetes Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Rou Shi ◽  
Yingjian Chen ◽  
Yuanjun Liao ◽  
Rang Li ◽  
Chunwen Lin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Noncoding Rnas ◽  
Vascular Complications ◽  
Differentially Expressed ◽  
Circular Rnas

Aims. Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. Methods. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA–miRNA and circRNA–miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE–RAGE signaling pathways of diabetic complications. Results. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE–RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE–RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Conclusion. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.

Circular RNAs as biomarkers in liquid biopsy in colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 230-230
Author(s):  
Manuel Valladares-Ayerbes ◽  
Carmen Garrigos ◽  
Miquel Taron ◽  
Angélica Figueroa ◽  
Enrique Aranda
Keyword(s):  
Colorectal Cancer ◽  
Bone Marrow ◽  
Expression Pattern ◽  
Liquid Biopsy ◽  
Expression Patterns ◽  
Target Prediction ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Blood Leukocytes ◽  
Specific Expression

230 Background: Circular RNAs (circRNAs) are emerging as essential regulators of cancer- related biological hallmarks, as cell proliferation, apoptosis, differentiation, immune regulation and angiogenesis. CircRNAs are abundant, conserved, and have a tissue‐specific expression pattern. These characteristics make them candidate to serve as biomarkers in liquid biopsy (LB) in cancer. The aim of this study is to analyse differential expression of circRNAs in the colorectal cancer (CRC) scenario. Methods: To comprehensively understand the expression patterns of circRNAs we characterized 13,617 circRNAs using a microarray [Arraystar v2 (8x15K)] in 10 human samples, five CRC cell lines, one colorectal human tumour, one normal colon healthy control, vs. Peripheral Human Blood Leukocytes (2 pools) and Human Bone Marrow. Differentially expressed circRNAs were identified using fold change (FC) cut-off or through Volcano Plot filtering respectively. CircRNAs having FC ▪2 and P-values ▪ 0.05 were selected. CircRNA/microRNA interaction was predicted with target prediction software. Results: Hierarchical clustering showed distinguishable circRNA expression profiling among 10 samples. These data indicated that circRNAs have a different expression pattern in colorectal tissues compared with that in blood and bone marrow tissues. The microarray data showed 2329 circRNAs differentially expressed (FC > 2.0, P < 0.05). Among them, 964 circRNAs were upregulated and 1365 were downregulated in colon tissues compared with blood and bone marrow. Using a stringent criterion (FC > 10, P≤ 0.01 and false discovery rate [FDR] < 0.05) we have identified 30 circRNA upregulated in colorectal cancer versus non tumour samples. CircRNA/microRNA interaction prediction analysis showed that most upregulated circRNAs contain miRNA Binding Sites (MREs) for cancer-related miRNA, including among others, miR-17, miR-103, miR-let-7g. Conclusions: Microarray analysis was used to comprehensively identify dysregulated circRNAs in CRC. We identify novel circRNAs could be valuable as blood-based CRC biomarkers.

scholarly journals Estrogen Receptor β: An Overview and Update

2008 ◽  
Vol 6 (1) ◽  
pp. nrs.06003 ◽  
Author(s):  
Chunyan Zhao ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Target Genes ◽  
Expression Patterns ◽  
Estrogen Signaling ◽  
Receptor Subtypes ◽  
Specific Expression ◽  
Microarray Experiments ◽  
Downstream Target ◽  
Animal Disease Models ◽  
Selective Ligands

The discovery of a second estrogen receptor (ER), designated ERβ (NR3A2), has redefined our knowledge about the mechanisms underlying cellular signaling by estrogens and has broad implications for our understanding of regulation of estrogen-responsive tissues. Highly variable and even contrasting effects of estrogens in different tissues seem to be at least partially explained by different estrogen signaling pathways, involving ERα (NR3A1) and/or ERβ. To date, two key conclusions can be drawn from the significant body of work carried out on the specific roles of the two receptor subtypes in diverse estrogen target tissues. First, ERα and ERβ have different biological functions, as indicated by their specific expression patterns and the distinct phenotypes observed in ERα and ERβ knockout (αERKO and βERKO) mice. Second, ERα and ERβ appear to have overlapping but also unique sets of downstream target genes, as judged from a set of microarray experiments. Thus, ERα and ERβ have different transcriptional activities in certain ligand, cell-type, and promoter contexts, which may help to explain some of the major differences in their tissue-specific biological actions. The phenotypes observed for βERKO mice have suggested certain therapeutic areas to be further explored. The development of ERβ-selective ligands active in animal disease models indicates new avenues for clinical exploration. ERβ agonists are being explored and validated as drugs for a growing number of indications. Hopefully, some ERβ targeted drugs will prove to be efficient in enhancing human health.

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