LncRNAs: emerging players in gene regulation and disease pathogenesis

Kazemzadeh, Mina; Safaralizadeh, Reza; Orang, Ayla Valinezhad

doi:10.1007/s12041-015-0561-6

Cited by 88 publications

(61 citation statements)

References 88 publications

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“…Yet, origins of lncRNAs are not well understood so far. Due to the fact that lncRNAs harbor low sequence conservations and rapid evolution among mammals, several evolutionary hypotheses could be proposed such as: (1) lncRNAs might be generated by the metamorphosis of protein-coding genes through a gene duplication process; (2) lncRNAs might have evolved from segmental or whole gene duplication of other ncRNA genes; (3) lncRNAs might have originated via de novo generation, such as alternations in genomes including chromosomal rearrangement, generation of splice sites and promoters might transform nonfunctional genomic sequences to functional lncRNAs; and (4) transposable elements (TEs) insertions might be another origin of lncRNAs (Ponting et al, 2009; Kaessmann, 2010; Kapusta et al, 2013; Kazemzadeh et al, 2015). However, it was observed that rarely or only a minority (~15%) of lncRNAs showed significant sequence similarity to other lncRNAs or protein-coding genes on positions other than the shared repetitive elements, suggesting that novel lncRNAs genes are basically originated rather from de novo non-exonic sequences and/or from TEs than duplication (Derrien et al, 2012; Kapusta et al, 2013).…”

Section: Characters and Functions Of Lncrnasmentioning

confidence: 99%

Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

Quan

Zheng

Qing

2017

Front. Cell. Neurosci.

104

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Accumulating studies have revealed that the human genome encodes tens of thousands of long non-coding RNAs (lncRNAs), which participate in multiple biological networks modulating gene expression via transcriptional, post-transcriptional and epigenetic regulation. Strikingly, a large fraction of tissue-specific lncRNAs are expressed in the Central Nervous System (CNS) with precisely regulated temporal and spatial expression patterns. These brain-specific lncRNAs are also featured with the cell-type specificity, the highest signals of evolutionary conservation, and their preferential location adjacent to brain-expressed protein-coding genes. Mounting evidence has indicated dysregulation or mutations in lncRNA gene loci are associated with a variety of CNS-associated neurodegenerative disorders, such as Alzheimer’s, Parkinson’s, Huntington’s diseases, Amyotrophic Lateral Sclerosis and others. However, how lncRNAs contribute to these disorders remains to be further explored and studied. In this review article, we systematically and comprehensively summarize the current studies of lncRNAs, demonstrate the specificity of lncRNAs expressed in the brain, their functions during neural development and expression profiles in major cell types of the CNS, highlight the regulatory mechanisms of several studied lncRNAs that may play essential roles in the pathophysiology of neurodegenerative diseases, and discuss the current challenges and future perspectives of lncRNA studies involved in neurodegenerative and other diseases.

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Section: Characters and Functions Of Lncrnasmentioning

confidence: 99%

Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

Quan

Zheng

Qing

2017

Front. Cell. Neurosci.

104

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“…Therefore, a better understanding of the pathogenesis and progression of RCC will require new therapies with improved outcomes. After miRNAs, lncRNAs have recently been implicated in many human disorders for their regulator roles; the dysregulation of lncRNAs serves as a causal factor in tumorigenesis and the progression of cancers [20] . As emerging stars in gene regulation, epigenetics, and human disease, lncRNAs have attracted much attention from researchers searching for the pathogenesis and best treatments for cancer.…”

Section: Discussionmentioning

confidence: 99%

LncRNA PCAT29 suppresses cell proliferation, invasion, and migration in renal carcinoma by regulating FLOT1

Sun

Luo

Zhong

et al. 2018

Clin Surg Res Commun

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Background: LncRNA PCAT29 has been reported to play a role in the development of cancer; the role of FLOT1 in renal carcinoma has been also identified. This study aimed at exploring the interaction between them and their influence on the progression of renal carcinoma. Methods: The expression levels of lncRNA PCAT29 and the FLOT1 protein in tissues were determined separately using qRT-PCR and western blot, respectively. The endogenous expression of genes was modulated by recombinant plasmid and cell transfection. The cell viability, invasion, and migration were detected by MTT assay, transwell assay, and wound-healing cell migration assay, respectively. Any binding and interactions between the RNA and the proteins were determined with RNA immunoprecipitation and RNA pull-down assays. A nude mouse model for renal carcinoma was established for the in vivo expression of PCAT29. Results: In renal carcinoma tissues, the expression of lncRNA PCAT29 was down-regulated while that of FLOT1 was up-regulated. PCAT29 negatively regulated FLOT1, and the overexpression of PCAT29 inhibited the cell proliferation viability, invasion, and migration of renal carcinoma by down-regulating FLOT1. The in vivo expression of PCAT29 inhibited tumor growth in a mouse model of renal carcinoma. Conclusion: LncRNA PCAT29 inhibited the cell proliferation viability, invasion, and migration in renal carcinoma by down-regulating FLOT1, thereby suppressing tumor growth.

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“…Based on proximal protein-coding mRNAs, lncRNAs have been classified as sense lncRNAs, antisense lncRNAs, intronic lncRNAs, bidirectional lncRNAs, and long intergenic ncRNAs (lincRNAs). LncRNAs have been shown to affect every stage of a gene's life cycle, including chromosome reconstruction, transcription, post-transcription, and intracellular metabolism [15][16][17][18]. In a recent study, the role of lncRNAs in the development of autoimmune diseases was highlighted [19].…”

Section: Introductionmentioning

confidence: 99%

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are important regulators of biological processes and they contribute to the pathological developments of various diseases, including autoimmune diseases. To gain the further understanding, we estimate the expression of lncRNAs in primary immune thrombocytopenia (ITP). Methods: In this study, microarray studies were performed to characterize expression profiles of various lncRNAs and mRNAs in blood samples collected from ITP patients. Quantitative real-time PCR (qRT-PCR) was performed to confirm the results, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene ontology analysis were used to provide functional annotations, co-expression network construction (CNC) analysis was made to reveal the relations between lncRNAs and their targeted genes. Results: A total of 1177 and 632 lncRNAs were significantly up-regulated or down-regulated, respectively, in “newly diagnosed ITP” patients versus healthy individuals. In addition, 1182 genes and 737 genes were up-regulated or down-regulated, respectively, in “chronic recurrent ITP” patients versus healthy individuals. In a KEGG analysis, “TNF signaling pathway-Homo sapiens (human)” was a key result. In a gene ontology analysis, “Granulocyte macrophage colony-stimulating factor production (GO: 0032604, ontology: Biological process, P = 1.69577E-05)” and “coreceptor activity (GO: 0015026, ontology: molecular function, P = 4.67594E-06)” were the two most critical results. Data from qRT-PCR and receiver operating characteristic curves further demonstrated that ENST00000440492, ENST00000528366, NR_038920, and ENST00000552576 can efficiently distinguish different stages of ITP, especially NR_038920 and ENST00000528366. In a CNC analysis, four lncRNAs were emphasized, and NR_038920 and ENST00000528366 were both associated with proteins with important roles in autoimmune diseases. Conclusions: These results suggest that lncRNAs act through targeted genes to mediate their functions and to mediate their functions and affect the pathogenesis of ITP.

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LncRNAs: emerging players in gene regulation and disease pathogenesis

Cited by 88 publications

References 88 publications

Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

Regulatory Roles of Long Non-Coding RNAs in the Central Nervous System and Associated Neurodegenerative Diseases

LncRNA PCAT29 suppresses cell proliferation, invasion, and migration in renal carcinoma by regulating FLOT1

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study

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