SP-0654 Transcriptional response to temozolomide in Glioblastoma reveals critical role of long non-coding RNAs

Over the last several decades, cardiovascular diseases largely increase the morbidity and mortality especially in developed countries, affecting millions of people worldwide. Although extensive work over the last two decades attempted to decipher the molecular network of regulating the pathogenesis and progression of these diseases, evidences from clinical trials with newly revealed targets failed to show more evidently salutary effects, indicating the inefficiency of understanding the complete regulatory landscape. Recent studies have shifted their focus from coding genes to the non-coding ones, which consist of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the lately re-discovered a unique group of RNAs—circular RNAs (circRNAs). As the focus now has been shifted to the newly identified group of non-coding RNAs, circRNAs exhibit stability, highly conservation and relative enriched expression abundance in some cases, which are distinct from their cognate linear counterparts—lncRNAs. So far, emerging evidence begins to support the critical role of circRNAs in organogenesis and pathogenesis as exemplified in the central nervous system, and could be just as implicative in the cardiovascular system, suggesting a therapeutic perspective in related diseases. Impact statement Circular RNAs are important regulators of multiple biological processes such as organogenesis and oncogenesis. Although the bulk of concerning studies focused on revealing their diversified roles in various types of cancers, reports began to accumulate in cardiovascular field these days. We summarize circular RNAs implicated in cardiovascular diseases, aiming to highlight the advances in the knowledge of such diseases and their potential of being promising target for diagnosis and therapy.

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A critical role for chromatin in mounting a synergistic transcriptional response to GAL4-VP16

Molecular and Cellular Biology ◽

10.1128/mcb.14.8.5175-5181.1994 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5175-5181

Author(s):

C Chang ◽

J D Gralla

Keyword(s):

Critical Role ◽

Transcriptional Response ◽

Dna Templates ◽

Naked Dna ◽

Promoter Dna

The role of chromatin in mounting a synergistic transcriptional response to GAL4-VP16 was investigated. Strong synergy was observed when chromatin templates were used in vitro. The synergy was severely reduced when naked DNA templates were transcribed. In vivo synergy was strong when nonreplicating templates were used. However, the use of replicating templates, which involved transient disruptions of chromatin, led to strong reductions in synergy. In both of these low-synergy responses, transcription levels were high. We infer that strong synergy has a requirement for chromatin that may be understood in terms of the competition between multiple activator molecules and histone cores for promoter DNA.

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The Critical Role of miRNAs in Regulation of Flowering Time and Flower Development

Genes ◽

10.3390/genes11030319 ◽

2020 ◽

Vol 11 (3) ◽

pp. 319

Author(s):

Saquib Waheed ◽

Lihui Zeng

Keyword(s):

Gene Expression ◽

Flower Development ◽

Critical Role ◽

Transcriptional Level ◽

Control Of Gene Expression ◽

Non Coding Rnas ◽

Time Of Year ◽

Acting In Concert ◽

Flowering Process

Flowering is an important biological process for plants that ensures reproductive success. The onset of flowering needs to be coordinated with an appropriate time of year, which requires tight control of gene expression acting in concert to form a regulatory network. MicroRNAs (miRNAs) are non-coding RNAs known as master modulators of gene expression at the post-transcriptional level. Many different miRNA families are involved in flowering-related processes such as the induction of floral competence, floral patterning, and the development of floral organs. This review highlights the diverse roles of miRNAs in controlling the flowering process and flower development, in combination with potential biotechnological applications for miRNAs implicated in flower regulation.

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The Emerging Role of Exosomal Non-coding RNAs in Musculoskeletal Diseases

Current Pharmaceutical Design ◽

10.2174/1381612825666191113104946 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4523-4535 ◽

Cited By ~ 5

Author(s):

Chao Tu ◽

Jieyu He ◽

Ruiqi Chen ◽

Zhihong Li

Keyword(s):

Musculoskeletal Diseases ◽

Critical Role ◽

Membrane Vesicles ◽

Phospholipid Bilayer ◽

Muscular Dystrophies ◽

Physiological Relevance ◽

Donor Cells ◽

Effective Delivery ◽

Non Coding Rnas

: Exosomes are phospholipid bilayer-enclosed membrane vesicles derived and constitutively secreted by various metabolically active cells. They are capable of mediating hetero- and homotypic intercellular communication by transferring multiple cargos from donor cells to recipient cells. Nowadays, non-coding RNAs (ncRNAs) have emerged as novel potential biomarkers or disease-targeting agents in a variety of diseases. However, the lack of effective delivery systems may impair their clinical application. Recently, accumulating evidence demonstrated that ncRNAs could be efficiently delivered to recipient cells using exosomes as a carrier, and therefore can exert a critical role in musculoskeletal diseases including osteoarthritis, rheumatoid arthritis, osteoporosis, muscular dystrophies, osteosarcoma and other diseases. Herein, we present an extensive review of biogenesis, physiological relevance and clinical implication of exosome-derived ncRNAs in musculoskeletal diseases.

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Transcriptomic Profiling of Fe-Responsive lncRNAs and Their Regulatory Mechanism in Rice

Genes ◽

10.3390/genes12040567 ◽

2021 ◽

Vol 12 (4) ◽

pp. 567

Author(s):

Shoudong Wang ◽

Shuo Sun ◽

Runze Guo ◽

Wenying Liao ◽

Huixia Shou

Keyword(s):

Regulatory Mechanism ◽

Transcriptional Response ◽

Fe Deficiency ◽

Rna Seq ◽

Systematic Screening ◽

Yield And Quality ◽

Non Coding Rnas ◽

Fe Homeostasis ◽

Insight Into

Iron (Fe) deficiency directly affects crop growth and development, ultimately resulting in reduced crop yield and quality. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to play critical regulatory roles in a multitude of pathways across numerous species. However, systematic screening of lncRNAs responding to Fe deficiency and their regulatory mechanism in plants has not been reported. In this work, 171 differently expressed lncRNAs (DE-lncRNAs) were identified based on analysis of strand-specific RNA-seq data from rice shoots and roots under Fe-deficient conditions. We also found several lncRNAs, which could generate miRNAs or act as endogenous target mimics to regulate expression of Fe-related genes. Analysis of interaction networks and gene ontology enrichment revealed that a number of DE-lncRNAs were associated with iron transport and photosynthesis, indicating a possible role of lncRNAs in regulation of Fe homeostasis. Moreover, we identified 76 potential lncRNA targets of OsbHLH156, a key regulator for transcriptional response to Fe deficiency. This study provides insight into the potential functions and regulatory mechanism of Fe-responsive lncRNAs and would be an initial and reference for any further studies regarding lncRNAs involved in Fe deficiency in plants.

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Analysis of the Small RNA Transcriptional Response in Multidrug-Resistant Staphylococcus aureus after Antimicrobial Exposure

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00263-13 ◽

2013 ◽

Vol 57 (8) ◽

pp. 3864-3874 ◽

Cited By ~ 50

Author(s):

Benjamin P. Howden ◽

Marie Beaume ◽

Paul F. Harrison ◽

David Hernandez ◽

Jacques Schrenzel ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Expression Profiles ◽

Critical Role ◽

Nonnegative Matrix ◽

Transcriptional Response ◽

Antibiotic Exposure ◽

Data Set ◽

Remarkable Feature ◽

Content Type

ABSTRACTThe critical role of noncoding small RNAs (sRNAs) in the bacterial response to changing conditions is increasingly recognized. However, a specific role for sRNAs during antibiotic exposure has not been investigated inStaphylococcus aureus. Here, we used Illumina RNA-Seq to examine the sRNA response of multiresistant sequence type 239 (ST239)S. aureusafter exposure to four antibiotics (vancomycin, linezolid, ceftobiprole, and tigecycline) representing the major classes of antimicrobials used to treat methicillin-resistantS. aureus(MRSA) infections. We identified 409 potential sRNAs and then compared global sRNA and mRNA expression profiles at 2 and 6 h, without antibiotic exposure and after exposure to each antibiotic, for a vancomycin-susceptible strain (JKD6009) and a vancomycin-intermediate strain (JKD6008). Exploration of this data set by multivariate analysis using a novel implementation of nonnegative matrix factorization (NMF) revealed very different responses for mRNA and sRNA. Where mRNA responses clustered with strain or growth phase conditions, the sRNA responses were predominantly linked to antibiotic exposure, including sRNA responses that were specific for particular antibiotics. A remarkable feature of the antimicrobial response was the prominence of antisense sRNAs to genes encoding proteins involved in protein synthesis and ribosomal function. This study has defined a large sRNA repertoire in epidemic ST239 MRSA and shown for the first time that a subset of sRNAs are part of a coordinated transcriptional response to specific antimicrobial exposures inS. aureus. These data provide a framework for interrogating the role of staphylococcal sRNAs in antimicrobial resistance and exploring new avenues for sRNA-based antimicrobial therapies.

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Emerging Role of microRNAs and Long Non-Coding RNAs in Sjögren’s Syndrome

Genes ◽

10.3390/genes12060903 ◽

2021 ◽

Vol 12 (6) ◽

pp. 903

Author(s):

Giada De Benedittis ◽

Cinzia Ciccacci ◽

Andrea Latini ◽

Lucia Novelli ◽

Giuseppe Novelli ◽

...

Keyword(s):

Environmental Factors ◽

Sjögren’S Syndrome ◽

Genetic Predisposition ◽

Sjögren's Syndrome ◽

Critical Role ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Non Coding Rnas ◽

Sjögren‘S Syndrome

Sjögren’s Syndrome (SS) is a chronic autoimmune inflammatory disease. It is considered a multifactorial pathology, in which underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to development. The epigenetic regulations represent a link between genetic predisposition and environmental factors. Recent studies suggested a regulatory role for non-coding RNAs in critical biological and disease processes. Among non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a critical role in the post-transcriptional mRNA expression, forming a complex network of gene expression regulation. This review aims to give an overview of the latest studies that have investigated the role of miRNAs and lncRNAs in the SS. We included papers that investigated the expression of non-coding RNAs on different tissues, in particular on peripheral blood mononuclear cells and salivary glands. However, regarding the involvement of non-coding RNAs genetic variability in SS susceptibility very few data are available. Further research could help to elucidate underlying pathogenic processes of SS and provide new opportunities for the development of targeted therapies.

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Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF

AJP Cell Physiology ◽

10.1152/ajpcell.1996.270.3.c803 ◽

1996 ◽

Vol 270 (3) ◽

pp. C803-C811 ◽

Cited By ~ 40

Author(s):

M. D. Roos ◽

I. O. Han ◽

A. J. Paterson ◽

J. E. Kudlow

Keyword(s):

Growth Factor ◽

Gene Transcription ◽

Transforming Growth Factor ◽

Critical Role ◽

Transcriptional Response ◽

Mrna Accumulation ◽

Glucose Signaling ◽

Alpha Gene ◽

Stimulation Of

Transforming growth factor-alpha (TGF-alpha) gene transcription is regulated by both epidermal growth factor (EGF) and glucose. Previous studies have suggested that the metabolism of glucose to glucosamine through the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase (GFAT) plays a critical role in the glucose signaling. In this paper, we compared the role of GFAT in the glucose and EGF signals. We found that, although EGF stimulates GFAT mRNA accumulation in MDA-MB-468 cells, this effect of EGF occurred several hours after TGF-alpha transcription increased. MDA-MB-468 cells also exhibited a TGF-alpha transcriptional response to low concentrations of glucose. The TGF-alpha response to glucose but not EGF could be inhibited by a blocker of GFAT activity. Blockade of GFAT was confirmed by using Western blotting with the RL2 antibody, which recognizes an epitope on proteins containing N-acetylglucosamine. Exposure of cells to glucose increased the RL2 signal on several polypeptides, but this change could be blocked by inhibition of GFAT. These results support the notion that glucose stimulation of TGF-alpha expression requires GFAT, but EGF stimulation does not.

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KCNQ1OT1 aggravates cell proliferation and migration in bladder cancer through modulating miR-145-5p/PCBP2 axis

Cancer Cell International ◽

10.1186/s12935-019-1039-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 8

Author(s):

Jingyu Wang ◽

Hao Zhang ◽

Jie Situ ◽

Mingzhao Li ◽

Hua Sun

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Apoptosis ◽

Critical Role ◽

Migration And Invasion ◽

Western Blot Assay ◽

Non Coding Rnas ◽

And Migration ◽

Proliferation And Migration

Abstract Background The large involvement of long non-coding RNAs (LncRNAs) in the biological progression of numerous cancers has been reported. The function of lncRNA KCNQ1OT1 in bladder cancer (BC) remains largely unknown. This study aimed to explore the critical role of KCNQ1OT1 in BC. Materials and methods The qRT-PCR was applied to test the expression of RNAs. Cell proliferation was detected by CCK-8 and colony formation assays. Cell apoptosis was measured by TUNEL and flow cytometry experiments. Wound healing and transwell assays were employed to evaluate cell migration and invasion ability respectively. Western blot assay was used to measure relevant protein expression. Immunofluorescence (IF) staining was used to observe EMT process in BC. Results KCNQ1OT1 was significantly overexpressed in BC tissue and cell lines. KCNQ1OT1 depletion repressed cell proliferation, migration and invasion, whereas encouraged cell apoptosis. KCNQ1OT1 was a negatively/positively correlated with miR-145-5p/PCBP2 in respect with expression. Mechanically, KCNQ1OT1 was sponge of miR-145-5p and up-regulated the expression of PCBP2. MiR-145-5p inhibition and PCBP2 up-regulation could countervail the tumor-inhibitor role of KCNQ1OT1 knockdown in BC. Conclusion KCNQ1OT1 serves as competing endogenous RNA (ceRNA) to up-regulate PCBP2 via sponging miR-145-5p in BC progression.

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Role of Pseudogenes in Tumorigenesis

Cancers ◽

10.3390/cancers10080256 ◽

2018 ◽

Vol 10 (8) ◽

pp. 256 ◽

Cited By ~ 29

Author(s):

Xinling Hu ◽

Liu Yang ◽

Yin-Yuan Mo

Keyword(s):

Critical Role ◽

Cellular Functions ◽

Protein Coding ◽

Master Regulators ◽

Protein Coding Genes ◽

The Past ◽

High Sequence Homology ◽

Regulation Mechanisms ◽

Non Coding Rnas

Functional genomics has provided evidence that the human genome transcribes a large number of non-coding genes in addition to protein-coding genes, including microRNAs and long non-coding RNAs (lncRNAs). Among the group of lncRNAs are pseudogenes that have not been paid attention in the past, compared to other members of lncRNAs. However, increasing evidence points the important role of pseudogenes in diverse cellular functions, and dysregulation of pseudogenes are often associated with various human diseases including cancer. Like other types of lncRNAs, pseudogenes can also function as master regulators for gene expression and thus, they can play a critical role in various aspects of tumorigenesis. In this review we discuss the latest developments in pseudogene research, focusing on how pseudogenes impact tumorigenesis through different gene regulation mechanisms. Given the high sequence homology with the corresponding parent genes, we also discuss challenges for pseudogene research.

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