scholarly journals The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130507 ◽  
Author(s):  
Thomas C. Roberts ◽  
Kevin V. Morris ◽  
Matthew J. A. Wood

Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed.

2013 ◽  
Vol 4 (4) ◽  
pp. 411-415 ◽  
Author(s):  
Nadia Vadaie ◽  
Kevin V. Morris

AbstractShortly after the completion of the human genome project in 2003, the Encode project was launched. The project was set out to identify the functional elements in the human genome, and unexpectedly it was found that >80% of the genome is transcribed. The Encode project identified those transcribed regions of the genome to be encoded by non-coding RNAs (ncRNAs). With only 2% of the genome carrying gene-encoding proteins, the conundrum was then, what is the function, if any, of these non-coding regions of the genome? These ncRNAs included both short and long RNAs. The focus of this review will be on antisense long non-coding RNAs (lncRNAs), as these transcripts have been observed to play a role in gene expression of protein-coding genes. Some lncRNAs have been found to regulate protein-coding gene transcription at the epigenetic level, whereby they suppress transcription through the recruitment of protein complexes to target loci in the genome. Conversely, there are lncRNAs that have a positive role in gene expression with less known about mechanism, and some lncRNAs have been shown to be involved in post-transcriptional processes. Additionally, lncRNAs have been observed to regulate their own expression in a positive feedback loop by functioning as a decoy. The biological significance of lncRNAs is only just now becoming evident, with many lncRNAs found to play a significant role in several human diseases.


2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.


2021 ◽  
Vol 22 (6) ◽  
pp. 3151 ◽  
Author(s):  
Roberto Piergentili ◽  
Simona Zaami ◽  
Anna Franca Cavaliere ◽  
Fabrizio Signore ◽  
Giovanni Scambia ◽  
...  

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.


2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Kun Guo ◽  
Wenbin Gong ◽  
Qin Wang ◽  
Guosheng Gu ◽  
Tao Zheng ◽  
...  

Abstract Long non-coding RNAs (lncRNAs) are essential contributors to the progression of various human cancers. Long intergenic non-protein coding RNA 1106 is a member of lncRNAs family. Until now, the specific role of LINC01106 in CRC remains undefined. The aim the current study was to unveil the functions of LINC01106 and explore its potential molecular mechanism in CRC. Based on the data of online database GEPIA, we determined that LINC01106 was expressed at a high level in colon adenocarcinoma (COAD) tissues compared to normal colon tissues. More importantly, high level of LINC01106 had negative correlation with the overall survival of COAD patients. Additionally, we also determined the low level of LINC01106 in normal colon tissues based on UCSC database. Through qRT-PCR, we identified that LINC01106 was highly expressed in CRC tissues compared to adjacent normal ones. Similarly, we detected the expression of LINC01106 and confirmed that LINC01106 was expressed higher in CRC cells than that in normal cells. Subsequently, LINC01106 was mainly distributed in the cytoplasm. LINC01106 induced the proliferation, migration, and stem-like phenotype of CRC cells. Mechanistically, cytoplasmic LINC01106 positively modulated Gli4 in CRC cells by serving as a miR-449b-5p sponge. Furthermore, nuclear LINC01106 could activate the transcription of Gli1 and Gli2 through recruiting FUS to Gli1 and Gli2 promoters. Mechanism of investigation unveiled that Gli2 was a transcription activator of LINC01106. In conclusion, Gli2-induced upregulation of LINC01106 aggravates CRC progression through upregulating Gli2, Gli2, and Gli4.


2018 ◽  
Vol 45 (3) ◽  
pp. 1191-1204 ◽  
Author(s):  
JingJing Wu ◽  
Swei Sunny Hann

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx and occurring at high frequency in South-eastern Asia and North Africa. Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNA molecules and key regulators of developmental, physiological, and pathological processes in humans. Emerging studies have shown that lncRNAs play critical roles in tumorgenicity and cancer prognosis. With the development of deep sequencing analyses, an extensive amount of functional lncRNAs have been discovered in nasopharyngeal carcinoma tissues and cell lines. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of NPC are not fully understood. In this review, we briefly illustrate the concept, identification, functional characterization, and summarize recent advancements of biological functions of lncRNAs with heterogeneous mechanistic characterization and their involvement in NPC. Then, we describe individual lncRNAs that have been associated with tumorgenesis, growth, invasion, cancer stem cell differentiation, metastasis, drug resistance and discuss the strategies of their therapeutic manipulation in NPC. We also review the emerging insights into the role of lncRNAs and their potential as biomarkers and therapeutic targets for novel treatment paradigms. Finally, we highlight the up-to-date of clinical information involving lncRNAs and future directions in the linking lncRNAs to potential gene therapies, and how modifications of lncRNAs can be exploited for prevention and treatment of NPC.


2019 ◽  
Vol 84 (6) ◽  
pp. 233-239
Author(s):  
Xu Hui ◽  
Hisham Al-Ward ◽  
Fahmi Shaher ◽  
Chun-Yang Liu ◽  
Ning Liu

<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.


Author(s):  
Chunying Zhang ◽  
Lin Yang ◽  
Ge Zhao ◽  
Jiaxiang Wang ◽  
Juntao Pan ◽  
...  

Neuroblastoma (NBL) exists as the most common solid malignancy which predominantly occurs in children. Long non-coding RNAs (lncRNAs) have been widely confirmed to exert functions in modulating the pathogenesis of diverse diseases. Nevertheless, whether the putative function of long intergenic non-protein coding RNA 1518 (LINC01518) in NBL has not been elucidated yet. In this study, RT-qPCR was used for determining LINC01518 expression and LINC01518 was found to be notably overexpressed in NBL tissues and cell lines compared with normal nerve tissues and cell lines. Functional experiments and mechanism assays were respectively done for the investigation into cell phenotype and for the exploration of correlation among genes. LINC01518 silencing was discovered to repress cell malignant phenotype. We observed that GATA binding protein 3 (GATA3) was an active transcription factor of LINC01518. Besides, LINC01518 functioned as a competing endogenous RNA (ceRNA), which sequestered microRNA-206 (miR-206) to up-regulate protein kinase cAMP-activated catalytic subunit beta (PRKACB). Afterwards, rescue assays validated the oncogenic role of GATA3/LINC01518/miR-206/PRKACB axis in NBL. To be summarized, our research determined that LINC01518 might be used as a putative molecular marker for NBL diagnosis and treatment.


Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5651
Author(s):  
Eleftheria Papaioannou ◽  
María del Pilar González-Molina ◽  
Ana M. Prieto-Muñoz ◽  
Laura Gámez-Reche ◽  
Alicia González-Martín

Cancer immunology research has mainly focused on the role of protein-coding genes in regulating immune responses to tumors. However, despite more than 70% of the human genome is transcribed, less than 2% encodes proteins. Many non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been identified as critical regulators of immune cell development and function, suggesting that they might play important roles in orchestrating immune responses against tumors. In this review, we summarize the scientific advances on the role of ncRNAs in regulating adaptive tumor immunity, and discuss their potential therapeutic value in the context of cancer immunotherapy.


2021 ◽  
Author(s):  
Louis Delhaye ◽  
Edith Bruycker ◽  
Pieter-Jan Volders ◽  
Daria Fijalkowska ◽  
Delphine Sutter ◽  
...  

Abstract Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, only very limited unbiased comprehensive approaches to map its interactome have been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting that HOTAIR has functions independent of its (post-)transcriptional mode-of-action.


2021 ◽  
Vol 12 ◽  
Author(s):  
Aadil Yousuf ◽  
Abrar Qurashi

Multiple sclerosis (MS) is an early onset chronic neurological condition in adults characterized by inflammation, demyelination, gliosis, and axonal loss in the central nervous system. The pathological cause of MS is complex and includes both genetic and environmental factors. Non-protein-coding RNAs (ncRNAs), specifically miRNAs and lncRNAs, are important regulators of various biological processes. Over the past decade, many studies have investigated both miRNAs and lncRNAs in patients with MS. Since then, insightful knowledge has been gained in this field. Here, we review the role of miRNAs and lncRNAs in MS pathogenesis and discuss their implications for diagnosis and treatment.


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