Long Non-Coding RNAs: A Novel Paradigm for Toxicology

Toxicological Sciences, Journal Year: 2016, Volume and Issue: 155(1), P. 3 - 21

Published: Oct. 11, 2016

Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and transcribed from the mammalian genome a tissue-specific developmentally regulated pattern. There is growing recognition that lncRNAs novel biomarkers and/or key regulators of toxicological responses humans animal models. Lacking protein-coding capacity, numerous types possess myriad transcriptional regulatory functions include cis trans gene expression, transcription factor activity, chromatin remodeling, imprinting, enhancer up-regulation. LncRNAs also influence mRNA processing, post-transcriptional regulation, protein trafficking. Dysregulation has been implicated various human health outcomes such as cancers, Alzheimer's disease, cardiovascular autoimmune diseases, well intermediary metabolism glucose, lipid, bile acid homeostasis. Interestingly, emerging evidence literature past five years shown lncRNA regulation impacted by exposures to chemicals polycyclic aromatic hydrocarbons, benzene, cadmium, chlorpyrifos-methyl, bisphenol A, phthalates, phenols, acids. Recent technological advancements, including next-generation sequencing technologies computational algorithms, have enabled profiling functional characterizations on genomic scale. In this review, we summarize biogenesis general biological lncRNAs, highlight important roles diseases especially during xenobiotics, evaluate current methods for identifying aberrant expression molecular target interactions, discuss potential implement these tools address fundamental questions toxicology.

Language: Английский

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LncRNAs: key players and novel insights into diabetes mellitus

Oncotarget, Journal Year: 2017, Volume and Issue: 8(41), P. 71325 - 71341

Published: Aug. 4, 2017

// Xiaoyun He 1, 2, * , Chunlin Ou 3, Yanhua Xiao 1 Qing Han Hao Li 4 and Suxian Zhou Department of Endocrinology, Affiliated Hospital Guilin Medical University, 541001, China 2 Xiangya Hospital, Central South Changsha 410008, 3 Cancer Research Institute, 410078, Neurology, These authors contributed equally to this work share co-first Correspondence to: Zhou, email: [email protected] Keywords: LncRNAs, diabetes mellitus, pancreatic β cells, insulin resistance, epigenetic regulation Received: March 29, 2017 Accepted: July 19, Published: August 04, ABSTRACT Long non-coding RNAs (LncRNAs) are a class endogenous RNA molecules, which have transcribing length over 200 nt, lack complete functional open reading frame (ORF), rarely encode short peptide. Recent studies revealed that disruption LncRNAs levels correlates with several human diseases, including mellitus (DM), complex multifactorial metabolic disorder affecting more than 400 million people worldwide. emerging as pivotal regulators in various biological processes, the progression DM its associated complications, involving β-cell disorder, regulation, etc . Further investigation into mechanisms action will be great value thorough understanding pathogenesis. However, prior successful application further search for molecular biomarkers drug targets provide new strategy prevention, early diagnosis, therapy is warranted.

Language: Английский

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LncRNA ENST00113 promotes proliferation, survival, and migration by activating PI3K/Akt/mTOR signaling pathway in atherosclerosis

Medicine, Journal Year: 2018, Volume and Issue: 97(16), P. e0473 - e0473

Published: April 1, 2018

Background: Atherosclerosis is one of the most common cardiovascular disorders. The dysfunction vascular smooth muscle cells (VSMCs) and endothelial (ECs) are 2 key factors in formation atherosclerosis. This study aims to find strategies prevent VSMCs ECs for treatment Methods: We investigated expression patterns long noncoding RNAs (lncRNAs) pairs serum samples from both atherosclerosis patients healthy volunteers through microarray analysis. Then we selected up-regulated lncRNA ENAST00113 (lnc00113) further verify its roles VSMCs, human umbilical vein (HUVECs) transfected with small interfering RNA (siRNAs) (si-00113-1, si-00113-1) a negative control (si-NC) were cultured. MTT assay, Caspase 3 enzyme-linked immunosorbent assay (ELISA) wound healing performed evaluate whether lnc00113 had an effect on proliferation, apoptosis, migration ability. Further, correlation between PI3K/Akt/mTOR signaling pathway was explored. Results: Microarray results indicated that 243 lncRNAs 187 down-regulated. Therefore, chose ENST explore Real-time polymerase chain reaction (RT-qPCR) showed highly increased patients. In vitro experiment demonstrated down-regulation significantly suppressed HUVECs survival, migration. Furthermore, found protein expressions phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR), bcl-2 si-00113-1 or si-00113-2 dramatically decreased compared si-NC-transfected cells. However, total- PI3K (t-PI3K), total-Akt (t-Akt), total-mTOR (t-mTOR) not changed, indicating could activate Conclusions: finding identified important role promotes cell by activating pathway, which probably serve as promising therapeutic target

Language: Английский

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Non-coding RNAs: key regulators of smooth muscle cell fate in vascular disease

Cardiovascular Research, Journal Year: 2017, Volume and Issue: 114(4), P. 611 - 621

Published: Dec. 28, 2017

The vascular smooth muscle cell (SMC) is one of the most plastic cells in body. Understanding how non-coding RNAs (ncRNAs) regulate SMC cell-fate decision making vasculature has significantly enhanced our understanding disease development, and opened up exciting new avenues for potential therapeutic applications. Recent studies on physiology have addition challenged traditional view their role contribution to disease, mainly setting atherosclerosis as well aneurysm restenosis after angioplasties. impact behaviour now recognized be context dependent; proliferation migration can harmful or beneficial, whereas apoptosis, senescence, switching into a more macrophage-like phenotype promote inflammation progression. This particular true atherosclerosis-related diseases, where SMCs was believed lesion formation, but may also prevent plaque rupture by stabilizing fibrous cap. Based newer findings genetic lineage tracing studies, it revealed that phenotypic result less-differentiated forms lack classical markers while exhibiting functions related cells. directly atherogenesis. aim this current review summarize discuss ncRNAs (mainly microRNAs long ncRNAs) are involved plasticity, they affect development Finally, we want critically assess future therapies could useful influence burden diseases.

Language: Английский

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Long noncoding RNAs in lipid metabolism: literature review and conservation analysis across species

BMC Genomics, Journal Year: 2019, Volume and Issue: 20(1)

Published: Nov. 21, 2019

Abstract Background Lipids are important for the cell and organism life since they major components of membranes, energy reserves also signal molecules. The main organs synthesis storage liver adipose tissue, both in humans more distant species such as chicken. Long noncoding RNAs (lncRNAs) known to be involved many biological processes including lipid metabolism. Results In this context, paper provides most exhaustive list lncRNAs metabolism with 60 genes identified after an in-depth analysis bibliography, while all “review” type articles a total 27 genes. These mainly described human or mice only few them have precise mode-of-action. Because these still named non-standard way making study tedious, we propose standard name according rules dictated by HUGO consortium. Moreover, about 10% which conserved between mammals chicken 2% fishes. Finally, demonstrated that two lncRNA were wrongly considered literature 3′ extensions closest coding gene. Conclusions Such catalogue can participate understanding regulators; it useful better understand genetic regulation some diseases (obesity, hepatic steatosis) traits economic interest livestock (meat quality, carcass composition). We no doubt first set will rapidly enriched coming years.

Language: Английский

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