Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets.
Ontology highlight
ABSTRACT:
SUBMITTER: Ray RM
PROVIDER: S-EPMC7151623 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets.
Ray Roslyn M RM Morris Kevin V KV
Non-coding RNA 20200313 1
This review aims to highlight the role of long non-coding RNAs in mediating human immunodeficiency virus (HIV-1) viral replication, latency, disease susceptibility and progression. In particular, we focus on identifying possible lncRNA targets and their purported mechanisms of action for future drug design or gene therapeutics. ...[more]
Similar Datasets
Project description:BackgroundThe problem of ischemic stroke (IS) has become increasingly important in recent years, as it ranks first in the structure of disability and mortality, crowding out other vascular diseases. In this regard, the study of this pathology and the search for new therapeutic and diagnostic tools remains an urgent problem of modern medical science and practice. Long non-coding RNAs (lncRNAs)-based therapeutics and diagnostic tools offer a very attractive area of study. Therefore, this systematic review aims at summarizing current knowledge on promising lncRNAs as biomarkers and therapeutic targets for IS exploring original articles and literature reviews on in vivo, in vitro and ex vivo experiments.MethodsThe current systematic review was performed according to PRISMA guidelines. PubMed, MEDLINE and Google Scholar databases were comprehensively explored to perform the article search.Results34 eligible studies were included and analyzed: 25 focused on lncRNAs-based therapeutics and 9 on lncRNAs-based diagnosis. We found 31 different lncRNAs tested as potential therapeutic and diagnostic molecules in cells and animal model experiments. Among all founded lncRNA-based therapeutics and non-invasive diagnostic tools, nuclear enriched abundant transcript 1 (NEAT1) emerged to be the most investigated and proposed as a potential molecule for IS diagnosis and treatment.ConclusionsOur analysis provides a snapshot of the current scenario regarding the lncRNAs as therapeutic molecules and biomarkers in IS. Different lncRNAs are differently expressed in IS, and some of them can be further evaluated as therapeutic targets and biomarkers for early diagnosis and prognosis or treatment response. However, despite many efforts, none of the selected studies go beyond preclinical studies, and their translation into clinical practice seems to be very premature.
| S-EPMC9508273 | biostudies-literature
Project description:Juvenile myelomonocytic leukemia (JMML) treatment primarily relies on hematopoietic stem cell transplantation and results in long-term overall survival of 50-60%, demonstrating a need to develop novel treatments. Dysregulation of the non-coding RNA transcriptome has been demonstrated before in this rare and unique disorder of early childhood. In this study, we investigated the therapeutic potential of targeting overexpressed long non-coding RNAs (lncRNAs) in JMML. Total RNA sequencing of bone marrow and peripheral blood mononuclear cell preparations from 19 untreated JMML patients and three healthy children revealed 185 differentially expressed lncRNA genes (131 up- and 54 downregulated). LNA GapmeRs were designed for 10 overexpressed and validated lncRNAs. Molecular knockdown (≥ 70% compared to mock control) after 24 h of incubation was observed with two or more independent GapmeRs in 6 of them. For three lncRNAs (lnc-THADA-4, lnc-ACOT9-1 and NRIR) knockdown resulted in a significant decrease of cell viability after 72 h of incubation in primary cultures of JMML mononuclear cells, respectively. Importantly, the extent of cellular damage correlated with the expression level of the lncRNA of interest. In conclusion, we demonstrated in primary JMML cell cultures that knockdown of overexpressed lncRNAs such as lnc-THADA-4, lnc-ACOT9-1 and NRIR may be a feasible therapeutic strategy.
| S-EPMC7854679 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are potent regulators of immune cell development and function. Their implication in multiple immune-mediated disorders highlights lncRNAs as exciting biomarkers and potential drug targets. Recent technological innovations in oligo-based therapeutics, development of RNA-targeting small molecules, and CRISPR-based approaches, position RNA as the next therapeutic frontier. Here, we review the latest advances made toward understanding the role of lncRNAs in human immunological disorders and further discuss RNA-targeting approaches that could be potentially exploited to manipulate lncRNA function as a clinical intervention.
| S-EPMC7150622 | biostudies-literature
Project description:Cervical cancer is the second most common cancer in women. The detection of oncopathologies in the early stages of development is a paramount task of modern medicine, which can be solved only by improving modern diagnostic methods. The use of screening for certain tumor markers could complement modern tests such as testing for oncogenic types of human papillomavirus (HPV), cytology, colposcopy with acetic acid and iodine solutions. Such highly informative biomarkers can be long noncoding RNAs (lncRNAs) that are highly specific compared to the mRNA profile and are involved in the regulation of gene expression. LncRNAs are a class of non-coding RNAs molecules that are typically over 200 nucleotides in length. LncRNAs may be involved in the regulation of all major cellular processes, including proliferation and differentiation, metabolism, signaling pathways, and apoptosis. LncRNAs molecules are highly stable due to their small size, which is also their undoubted advantage. The study of individual lncRNAs as regulators of the expression of genes involved in the mechanisms of oncogenesis cervical cancer can be not only of great diagnostic value, but, as a result, of therapeutic significance in cervical cancer patients. This review article will present the characteristics of lncRNAs that allow them to be used as accurate diagnostic and prognostic tools, as well as to consider them as effective therapeutic targets in cervical cancer.
| S-EPMC9988427 | biostudies-literature
Project description:Genomic imprinting is a term used for an intergenerational epigenetic inheritance and involves a subset of genes expressed in a parent-of-origin-dependent way. Imprinted genes are expressed preferentially from either the paternally or maternally inherited allele. Long non-coding RNAs play essential roles in regulating this allele-specific expression. In several well-studied imprinting clusters, long non-coding RNAs have been found to be essential in regulating temporal- and spatial-specific establishment and maintenance of imprinting patterns. Furthermore, recent insights into the epigenetic pathological mechanisms underlying human genomic imprinting disorders suggest that allele-specific expressed imprinted long non-coding RNAs serve as an upstream regulator of the expression of other protein-coding or non-coding imprinted genes in the same cluster. Aberrantly expressed long non-coding RNAs result in bi-allelic expression or silencing of neighboring imprinted genes. Here, we review the emerging roles of long non-coding RNAs in regulating the expression of imprinted genes, especially in human imprinting disorders, and discuss three strategies targeting the central long non-coding RNA UBE3A-ATS for the purpose of developing therapies for the imprinting disorders Prader-Willi syndrome and Angelman syndrome. In summary, a better understanding of long non-coding RNA-related mechanisms is key to the development of potential therapeutic targets for human imprinting disorders.
| S-EPMC8573313 | biostudies-literature
Project description:Recent technological advancements such as CRISPR/Cas-based systems enable multiplexed, high-throughput screening for new therapeutic targets in cancer. While numerous functional screens have been performed on protein-coding genes to date, long non-coding RNAs (lncRNAs) represent an emerging class of potential oncogenes and tumor suppressors, with only a handful of large-scale screens performed thus far. Here, we review in detail currently available screening approaches to identify new lncRNA drivers of tumorigenesis and tumor progression. We discuss the various approaches of genomic and transcriptional targeting using CRISPR/Cas9, as well as methods to post-transcriptionally target lncRNAs via RNA interference (RNAi), antisense oligonucleotides (ASOs) and CRISPR/Cas13. We discuss potential advantages, caveats and future applications of each method to provide an overview and guide on investigating lncRNAs as new therapeutic targets in cancer.
| S-EPMC7763270 | biostudies-literature
Project description:Gliomas are the most common malignancies of the central nervous system. Because of tumor localization and the biological behavior of tumor cells, gliomas are characterized by very poor prognosis. Despite significant efforts that have gone into glioma research in recent years, the therapeutic efficacy of available treatment options is still limited, and only a few clinically usable diagnostic biomarkers are available. More and more studies suggest non-coding RNAs to be promising diagnostic biomarkers and therapeutic targets in many cancers, including gliomas. One of the largest groups of these molecules is long non-coding RNAs (lncRNAs). LncRNAs show promising potential because of their unique tissue expression patterns and regulatory functions in cancer cells. Understanding the role of lncRNAs in gliomas may lead to discovery of the novel molecular mechanisms behind glioma biological features. It may also enable development of new solutions to overcome the greatest obstacles in therapy of glioma patients. In this review, we summarize the current knowledge about lncRNAs and their involvement in the molecular pathology of gliomas. A conclusion follows that these RNAs show great potential to serve as powerful diagnostic, prognostic, and predictive biomarkers as well as therapeutic targets.
| S-EPMC6163683 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are generally defined as RNA molecules greater than 200 nt in length and without protein-coding property that different from housekeeping RNAs such as tRNAs, rRNAs, and snRNAs, and independent from small RNAs with specific molecular processing machinery such as micro- or piwi-RNAs. LncRNAs are a novel class of mRNA-like transcripts which contribute to cancer development and progression and accelerate cancer cells proliferation, invasion, metastasis, and apoptosis. These research results indicate the potential of lncRNAs as prospective novel biomarkers for diagnosis, therapeutic targets and prognosis for cancers. In this review, we synthesize present study results to highlight aberration of lncRNAs in various types of head and neck cancers, and try to clarify the molecular mechanisms of lncRNAs affecting the oncogenesis and progression of head and neck cancer, as well as pay particular attention to provide a new avenue to the diagnosis and treatment strategy.
| S-EPMC4014209 | biostudies-literature
Project description:The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naïve T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection.
| S-EPMC6844474 | biostudies-literature
Project description:Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.
| S-EPMC5522170 | biostudies-other