Therapeutic targeting of non-coding RNAs

2013 ◽  
Vol 54 ◽  
pp. 127-145 ◽  
Author(s):  
Thomas C. Roberts ◽  
Matthew J.A. Wood
Keyword(s):  
Gene Expression ◽  
Antisense Oligonucleotides ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Mature Mirnas ◽  
Transcriptional Gene Silencing ◽  
Small Interfering Rnas ◽  
Promising Therapeutic Approach ◽  
Non Coding Rnas ◽  
Mirna Sponges

ncRNAs (non-coding RNAs) are implicated in a wide variety of cellular processes, including the regulation of gene expression. In the present chapter we consider two classes of ncRNA: miRNAs (microRNAs) which are post-transcriptional regulators of gene expression and lncRNAs (long ncRNAs) which mediate interactions between epigenetic remodelling complexes and chromatin. Mutation and misexpression of ncRNAs have been implicated in many disease conditions and, as such, pharmacological modulation of ncRNAs is a promising therapeutic approach. miRNA activity can be antagonized with antisense oligonucleotides which sequester or degrade mature miRNAs, and expressed miRNA sponges which compete with target transcripts for miRNA binding. Conversely, synthetic or expressed miRNA mimics can be used to treat a deficiency in miRNA expression. Similarly, conventional antisense technologies can be used to silence lncRNAs. Targeting promoter-associated RNAs with siRNAs (small interfering RNAs) results in recruitment of chromatin-modifying activities and induces transcriptional gene silencing. Alternatively, targeting natural antisense transcripts with siRNAs or antisense oligonucleotides can abrogate endogenous epigenetic silencing leading to transcriptional gene activation. The ability to modulate gene expression at the epigenetic level presents exciting new opportunities for the treatment of human disease.

scholarly journals Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhang-Wei Liu ◽  
Nan Zhao ◽  
Yin-Na Su ◽  
Shan-Shan Chen ◽  
Xin-Jian He
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Histone Mark ◽  
Repressive Histone Mark ◽  
Enhanced Expression ◽  
Non Coding Rnas ◽  
Active Histone Mark ◽  
Affect Gene Expression ◽  
Host Genes

AbstractInvolvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression in cis has been well studied in eukaryotes but relatively little is known whether and how lncRNAs affect gene expression in tans. In Arabidopsis thaliana, COLDAIR, a previously reported lncRNA, is produced from the first intron of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering time. Our results indicated that the exogenously overexpressed COLDAIR enhances the expression of FLC in trans, resulting in a late-flowering phenotype. In 35S-COLDAIR lines, the enhanced expression of FLC is correlated with the down-regulation of the repressive histone mark H3K27me3 and with the up-regulation of the active histone mark H3K4me3 at the FLC chromatin. Furthermore, we demonstrated that overexpression of intronic lncRNAs from several other H3K27me3-enriched MADS-box genes also activates the expression of their host genes. This study suggests that the involvement of overexpressed intronic lncRNAs in gene activation may be conserved in H3K27me3-enriched genes in eukaryotes.

scholarly journals Long non-coding RNAs in brain tumors

NAR Cancer ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Keisuke Katsushima ◽  
George Jallo ◽  
Charles G Eberhart ◽  
Ranjan J Perera
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Brain Cancer ◽  
Regulation Of Gene Expression ◽  
Therapeutic Targets ◽  
Diagnostic Biomarkers ◽  
Cancer Pathogenesis ◽  
Current State ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Abstract Long non-coding RNAs (lncRNAs) have been found to be central players in the epigenetic, transcriptional and post-transcriptional regulation of gene expression. There is an accumulation of evidence on newly discovered lncRNAs, their molecular interactions and their roles in the development and progression of human brain tumors. LncRNAs can have either tumor suppressive or oncogenic functions in different brain cancers, making them attractive therapeutic targets and biomarkers for personalized therapy and precision diagnostics. Here, we summarize the current state of knowledge of the lncRNAs that have been implicated in brain cancer pathogenesis, particularly in gliomas and medulloblastomas. We discuss their epigenetic regulation as well as the prospects of using lncRNAs as diagnostic biomarkers and therapeutic targets in patients with brain tumors.

The Role of miR-210 in the Biological System: A Current Overview

2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Low Oxygen ◽  
Cellular Functions ◽  
Regulate Gene Expression ◽  
System A ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
A Current

<b><i>Background:</i></b> MicroRNAs (miRNAs) represent a group of non-coding RNAs measuring 19–23 nucleotides in length and are recognized as powerful molecules that regulate gene expression in eukaryotic cells. miRNAs stimulate the post-transcriptional regulation of gene expression via direct or indirect mechanisms. <b><i>Summary:</i></b> miR-210 is highly upregulated in cells under hypoxia, thereby revealing its significance to cell endurance. Induction of this mRNA expression is an important feature of the cellular low-oxygen response and the most consistent and vigorous target of HIF. <b><i>Key Message:</i></b> miR-210 is involved in many cellular functions under the effect of HIF-1α, including the cell cycle, DNA repair, immunity and inflammation, angiogenesis, metabolism, and macrophage regulation. It also plays an important regulatory role in T-cell differentiation and stimulation.

scholarly journals Pbx1 Represses Osteoblastogenesis by Blocking Hoxa10-Mediated Recruitment of Chromatin Remodeling Factors

2010 ◽  
Vol 30 (14) ◽  
pp. 3531-3541 ◽  
Author(s):  
Jonathan A. R. Gordon ◽  
Mohammad Q. Hassan ◽  
Sharanjot Saini ◽  
Martin Montecino ◽  
Andre J. van Wijnen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylases ◽  
Skeletal Development ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Gene Promoters ◽  
Homeodomain Proteins ◽  
Temporal Regulation ◽  
Multipotent Cells ◽  
P300 Recruitment

ABSTRACT Abdominal-class homeodomain-containing (Hox) factors form multimeric complexes with TALE-class homeodomain proteins (Pbx, Meis) to regulate tissue morphogenesis and skeletal development. Here we have established that Pbx1 negatively regulates Hoxa10-mediated gene transcription in mesenchymal cells and identified components of a Pbx1 complex associated with genes in osteoblasts. Expression of Pbx1 impaired osteogenic commitment of C3H10T1/2 multipotent cells and differentiation of MC3T3-E1 preosteoblasts. Conversely, targeted depletion of Pbx1 by short hairpin RNA (shRNA) increased expression of osteoblast-related genes. Studies using wild-type and mutated osteocalcin and Bsp promoters revealed that Pbx1 acts through a Pbx-binding site that is required to attenuate gene activation by Hoxa10. Chromatin-associated Pbx1 and Hoxa10 were present at osteoblast-related gene promoters preceding gene expression, but only Hoxa10 was associated with these promoters during transcription. Our results show that Pbx1 is associated with histone deacetylases normally linked with chromatin inactivation. Loss of Pbx1 from osteoblast promoters in differentiated osteoblasts was associated with increased histone acetylation and CBP/p300 recruitment, as well as decreased H3K9 methylation. We propose that Pbx1 plays a central role in attenuating the ability of Hoxa10 to activate osteoblast-related genes in order to establish temporal regulation of gene expression during osteogenesis.

Misregulation of the Dependence Receptor DCC and its Upstream lincRNA, LOC100287225, in Colorectal Cancer

2015 ◽  
Vol 103 (1) ◽  
pp. 40-43 ◽  
Author(s):  
Mina Kazemzadeh ◽  
Reza Safaralizadeh ◽  
Mohammad Ali HosseinPour feizi ◽  
Mohammad Hossein Somi ◽  
Behrooz Shokoohi
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Regulation Of Gene Expression ◽  
Cellular Processes ◽  
Qrt Pcr ◽  
Cis Regulation ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Colorectal Cancer Patients ◽  
Dependence Receptor

Background Long non-coding RNAs (lncRNAs), a class of regulatory RNAs, play a major role in various cellular processes. Long intergenic non-coding RNAs (lincRNAs), a subclass of lncRNAs, are involved in the trans- and cis-regulation of gene expression. In the case of cis-regulation, by recruiting chromatin-modifying complexes, lincRNAs influence adjacent gene expression. Methods We used quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to evaluate the coexpression of LOC100287225, a lincRNA, and DCC, one of its adjacent genes that is often decreased in colorectal cancer, in pairs of tumor and adjacent tumor-free tissues of 30 colorectal cancer patients. Results The qRT-PCR results revealed the misregulation of these genes during tumorigenesis. Their relative expression levels were significantly lower in tumor tissues than adjacent tumor-free tissues. However, the analysis found no significant correlation between reduced expression of these genes. Conclusions Our study demonstrated the concurrent misregulation of DCC and LOC100287225 in colorectal cancer.

scholarly journals Circular RNAs in Cardiovascular Disease: An Overview

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Ximin Fan ◽  
Xinyu Weng ◽  
Yifan Zhao ◽  
Wei Chen ◽  
Tianyi Gan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Noncoding Rna ◽  
Essential Role ◽  
Closed Loop ◽  
Regulation Of Gene Expression ◽  
Circular Rna ◽  
Circular Rnas ◽  
Mirna Sponges

Circular RNA (circRNA), a novel type of endogenous noncoding RNA (ncRNA), has become a research hotspot in recent years. CircRNAs are abundant and stably exist in creatures, and they are found with covalently closed loop structures in which they are quite different from linear RNAs. Nowadays, an increasing number of scientists have demonstrated that circRNAs may have played an essential role in the regulation of gene expression, especially acting as miRNA sponges, and have described the potential mechanisms of several circRNAs in diseases, hinting at their clinical therapeutic values. In this review, the authors summarized the current understandings of the biogenesis and properties of circRNAs and their functions and role as biomarkers in cardiovascular diseases.

scholarly journals Cis-directed cleavage and nonstoichiometric abundances of 21-nt reproductive phasiRNAs in grasses

2018 ◽  
Author(s):  
Saleh Tamim ◽  
Zhaoxia Cai ◽  
Sandra Mathioni ◽  
Jixian Zhai ◽  
Chong Teng ◽  
...  
Keyword(s):  
Computational Analysis ◽  
Developmental Stages ◽  
Transcriptional Gene Silencing ◽  
List Type ◽  
Small Interfering Rnas ◽  
Regulatory Activity ◽  
Sequence Composition ◽  
Post Transcriptional Gene Silencing ◽  
Non Coding Rnas ◽  
Weak Accumulation

SummaryPost-transcriptional gene silencing in plants results from independent activities of diverse small RNA types. In anthers of grasses, hundreds of loci yield non-coding RNAs that are processed into 21- and 24-nt phased small interfering RNAs (phasiRNAs); these are triggered by miR2118 and miR2275.We characterized these “reproductive phasiRNAs” from rice panicles and anthers across seven developmental stages. Our computational analysis identified characteristics of the 21-nt reproductive phasiRNAs that impact their biogenesis, stability, and potential functions.We demonstrate that 21-nt reproductive phasiRNAs can function in cis to target their own precursors. We observed evidence of this cis regulatory activity in both rice (Oryza sativa) and maize (Zea mays). We validated this activity with evidence of cleavage and a resulting shift in the pattern of phasiRNA production.We characterize biases in phasiRNA biogenesis, demonstrating that the Pol II-derived “top” strand phasiRNAs are consistently higher abundance than the bottom strand. The first phasiRNA from each precursor overlaps the miR2118 target site, and this impacts phasiRNA accumulation or stability, evident in the weak accumulation of this phasiRNA position. Additional influences on this first phasiRNA duplex include the sequence composition and length, and we show that these factors impact Argonaute loading.

scholarly journals The involvement of human endogenous retroviruses K (HERV-K) in aging processes via induction of inflammation

2019 ◽  
Author(s):  
Chingis Ochirov
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Endogenous Retroviruses ◽  
Human Organism ◽  
Human Endogenous Retroviruses ◽  
Regulate Gene Expression ◽  
Spontaneous Transition ◽  
Developmental Program ◽  
Non Coding Rnas ◽  
Insight Into

This detailed analysis provides an insight into aging processes in the human organism. The developmental program that controls the regulation of gene expression through epigenetic modifications leads to cellular senescence in the latter life. This epigenetic development system uses endogenous retroviruses and other retrotransposons as control elements that regulate gene expression through non-coding RNAs. Interaction with sex hormones causes activation of human endogenous retroviruses K (HERV-K) inducing a prolonged innate immune response and therefore chronic inflammation leading to complex changes in the signaling pathways inside the cell and thus contributes to age-associated phenotype in the form of tissue deterioration and may cause a spontaneous transition of tissues to cancer state.

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