Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

Plewka, Patrycja; Raczyńska, Katarzyna Dorota

doi:10.1007/s12035-022-02941-0

Cited by 9 publications

(3 citation statements)

References 159 publications

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“…MEG8 is a member of a lncRNA cluster, including MEG3 and MEG9 , involved in the response to glycine stimulation in a N-methyl-d-aspartate glutamate receptors (NMDAR)-dependent manner in a murine model ( Tan et al, 2017 ) and this is relevant because the NMDA signaling is impaired in AD ( Dore et al, 2017 ). MEG9 has been recently reported to be downregulated in AD hippocampus ( Wang et al, 2022 ) and involved in the pathogenesis of autoimmune and neurodegenerative diseases ( Plewka and Raczynska, 2022 ). Regarding PCA3 , it was extensively studied in cancer ( Lemos et al, 2019 ) and was found to be differentially expressed in the exosomes of cerebrospinal fluid of AD patients ( Gui et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

Filomena,

Picardi,

Tullo

et al. 2024

Front. Aging Neurosci.

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IntroductionThe deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer’s disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls.MethodsWe performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets.ResultsWe found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions.DiscussionWe found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD.

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Section: Discussionmentioning

confidence: 99%

Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

Filomena,

Picardi,

Tullo

et al. 2024

Front. Aging Neurosci.

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“…An aberrant expression of HERVs associates with chronic inflammatory or degenerative diseases of the nervous system, such as multiple sclerosis, amyotrophic lateral sclerosis (ALS), or schizophrenia as well as with cancer progression 46,47 . Likewise, mutations of lincRNAs or their deregulation have been linked to tumorigenesis and genetically inherited diseases 18,28,48 . Unfortunately, U7-dependent lincRNAs and HERV1/LTR12s are poorly studied, and their function remains a mystery.…”

Section: Disscussion U7 Snrna Acts As a Transcription Inhibitor To Pr...mentioning

confidence: 99%

Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells

Plewka,

Szczesniak,

Pasieka

et al. 2023

Preprint

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U7 snRNA is part of U7 snRNP, a complex required for the 3'end processing of replication-dependent histone pre-mRNAs in the S phase of the cell cycle. During this maturation event, the 5' region of U7 snRNA hybridizes with the highly complementary sequence present in the 3'UTR of histone pre-mRNAs, called histone downstream element, HDE. This base-pair interaction triggers subsequent reactions that eventually result in cleavage and release of mature histone transcripts. Intriguingly, U7 snRNP is constitutively expressed throughout the cell cycle and in nondividing cells, suggesting another function of U7 snRNA/snRNP in cells. Here, we show that several human endogenous retroviruses (HERVs) are significantly upregulated in HEK293T cells with U7 snRNA knockdown. They predominantly belong to the LTR12 class. Interestingly, some of them are located within long intergenic noncoding RNAs (lincRNAs), which in turn are upregulated in U7 snRNA knockdown cells as well. Significantly, both these HERV1/LTR12s and lincRNAs contain two or more sequence motifs that perfectly match the 5' end of U7 snRNA, which we called HDE-like motifs. We confirmed that mutations within the HDE-like motifs abrogate U7 snRNA regulatory function and stimulate the expression of selected lincRNAs. Furthermore, we demonstrate that U7 snRNA inhibits HERV1/LTR12 and lincRNA expression at the transcription level. We propose a mechanism in which U7 snRNA hampers binding/activity of NF-Y transcription factor to CCAAT motifs that are frequently found in LTRs as well as in a close proximity to HDE-like motifs. The expression of many HERV1/LTR12s and lincRNAs regulated by U7 snRNA seems to be tissue specific, therefore, we suggest that U7 snRNA plays a protective role in keeping deleterious genetic elements in silence in selected types of cells.

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“…It is known that lincRNAs affect biological pathways in autoimmune and neurodegenerative disorders [ 10 ], cardiovascular diseases [ 9 ], inflammation [ 11 , 12 ], and normal and malignant hematopoiesis [ 13 ]. LincRNAs are aberrantly expressed in various malignant tumors [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Long Intergenic Non-Coding RNAs of Human Chromosome 18: Focus on Cancers

Ershov,

Yablokov,

Mezentsev

et al. 2024

Biomedicines

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Malignant neoplasms are characterized by high molecular heterogeneity due to multilevel deregulation of gene expression and cellular functions. It is known that non-coding RNAs, including long intergenic non-coding RNAs (lincRNAs), can play significant roles in cancer biology. The current review focuses on a systematical analysis of genomic, transcriptomic, epigenomic, interactomic, and literature data on 65 lincRNAs of human chromosome 18 in the context of pan-cancer studies. The entire group of lincRNAs can be conditionally divided into 4 subgroups depending on experimental evidence on direct or indirect involvement in cancers and the biological associations with cancers, which we found during the data-mining process: the most studied (5 lincRNAs), moderately or poorly studied (11 lincRNAs), and understudied (31 lincRNAs). For the remaining 18 lincRNAs, data for analysis were fragmentary or missing. Among the key findings were the following: Of the lincRNAs of human chromosome 18, 40% have tissue-specific expression patterns, 22% of lincRNAs are known to have gene fusions, 40% of lincRNAs are prone to gene amplifications and/or deletions in cancers at a frequency greater than 3%, and 23% of lincRNAs are differentially expressed across cancer types, whereas 7% have subtype-specific expression patterns. LincRNAs’ interactomes consist of ‘master’ microRNAs and 47 proteins (including cancer-associated proteins and microRNAs) that can interact with 3 or more lincRNAs. Functional enrichment analysis of a set of highly co-expressed genes retrieved for 17 lincRNAs in different cancer types indicated the potential associations of these lincRNAs with cellular signaling pathways. Six lincRNAs encoded small open-reading frame (smORF) proteins with emerging roles in cancers, and microRNAs as well as proteins with known functions in molecular carcinogenesis can bind to coding regions of smORFs. We identified seven transcriptomic signatures with potential prognostic value, consisting of two to seven different lincRNAs only. Taken together, the literature, biomedical, and molecular biology data analyzed indicated that only five of all lincRNAs of human chromosome 18 are cancer-associated, while eleven other lincRNAs have the tendency to be associated with cancers.

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Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

Cited by 9 publications

References 159 publications

Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

Identification of deregulated lncRNAs in Alzheimer’s disease: an integrated gene co-expression network analysis of hippocampus and fusiform gyrus RNA-seq datasets

Novel function of U7 snRNA in the repression of HERV1/LTR12s and lincRNAs in human cells

Long Intergenic Non-Coding RNAs of Human Chromosome 18: Focus on Cancers

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