LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF DOI Creative Commons

Shenrong Liu,

Haobin Zhou,

Dunzheng Han

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: April 10, 2024

Abstract Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral orchestrating various pathologies by modulating the phenotypic dynamics VSMCs. The influence CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk sequencing, has uncovered significant suppression specimens, which correlates strongly with contractile function This reduced expression was consistent both 7- 14-day porcine pancreatic elastase (PPE)-induced mouse models human clinical cases. Functional analyses disclosed that diminution exacerbated PPE-precipitated whereas augmentation conferred protection against such Mechanistically, we found CARMN's capacity to bind SRF, thereby amplifying driving transcription VSMC marker genes. In addition, our findings indicate an enhancement CAMRN transcription, facilitated binding NRF2 promoter region. study indicated protective preventing formation restrains through interaction SRF. Additionally, observed augmented These suggest potential as viable therapeutic target treatment AAA. Graphical abstract

Language: Английский

From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases DOI Open Access
Ulf Landmesser, Wolfgang Poller, Sotirios Tsimikas

et al.

European Heart Journal, Journal Year: 2020, Volume and Issue: 41(40), P. 3884 - 3899

Published: March 13, 2020

Abstract Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal CVD; (ii) there is a substantial recent progress in delivery, efficacy, safety nucleic therapies; (iii) they enable effective modulation that cannot sufficiently or optimally addressed using traditional small molecule drugs antibodies. include RNA-targeted gene silencing; microRNA-modulating epigenetic (iv) genome-editing approaches (e.g. CRISPR-Cas-based): therapeutics: several large-scale clinical development programmes, antisense oligonucleotides (ASO) short interfering RNA (siRNA) CVD been initiated. These ASO and/or siRNA molecules lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, transthyretin (TTR) treatment patients with atherosclerotic TTR amyloidosis. MicroRNA-modulating therapies: potential continually arising from human non-coding genome research. First microRNA-based therapies targeting regulatory pathways studies. Gene EMA/FDA approved non-cardiac monogenic LDL receptor therapy being examined homozygous hypercholesterolaemia. In experimental studies, has significantly improved cardiac function heart failure animal models. Genome editing approaches: these technologies, such as CRISPR-Cas, proven powerful stem cells, however, important challenges remaining, e.g. low rates homology-directed repair somatic cells cardiomyocytes. summary, apo(a)-ASO PCSK9-siRNA) now outcome trials will most likely become safe option the near future. MicroRNA-modulating, epigenetic, tested early CVD. CRISPR-Cas-mediated highly but major remaining this field rapidly advancing.

Language: Английский

Citations

80
The multifaceted actions of the lncRNA H19 in cardiovascular biology and diseases DOI Creative Commons
Denise Busscher, Reinier A. Boon, Rio P. Juni

et al.

Clinical Science, Journal Year: 2022, Volume and Issue: 136(15), P. 1157 - 1178

Published: Aug. 1, 2022

Abstract Cardiovascular diseases are the leading cause of death and debility worldwide. Various molecular mechanisms have been studied to better understand development progression cardiovascular pathologies with hope eradicate these diseases. With advancement sequencing technology, it is revealed that majority our genome non-coding. A growing body literature demonstrates critical role long non-coding RNAs (lncRNAs) as epigenetic regulators gene expression. LncRNAs can regulate cellular biological processes through various distinct mechanisms. The abundance lncRNAs in system indicates their significance physiology pathology. LncRNA H19, particular, a highly evolutionarily conserved lncRNA enriched cardiac vascular tissue, underlining its importance maintaining homeostasis system. In this review, we discuss versatile function H19 types We highlight current on demonstrate how dysregulation induces pathophysiology.

Language: Английский

Citations

44
Probing the links: Long non-coding RNAs and NF-κB signalling in atherosclerosis DOI
Md Sadique Hussain, Obaid Afzal, Gaurav Gupta

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154773 - 154773

Published: Aug. 18, 2023

Language: Английский

Citations

24
Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer DOI Creative Commons

Yuyang Xia,

Tianjiao Pei,

Junjie Zhao

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 14, 2024

Long noncoding RNAs (lncRNAs) are a group of with transcript lengths >200 nucleotides. Mounting evidence suggests that lncRNAs closely associated tumorigenesis. LncRNA H19 (H19) was the first lncRNA to function as an oncogene in many malignant tumors. Apart from established role promoting cell growth, proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and metastasis, it has been recently discovered also inhibits programmed death (PCD) cancer cells. In this review, we summarize mechanisms by which regulates PCD cells through various signaling pathways, molecular mechanisms, epigenetic modifications. Wnt/β-catenin pathway PI3K-Akt-mTOR pathway. It acts competitive endogenous RNA (ceRNA) regulation. The interaction between RNA-binding proteins (RBP) apoptosis cancer. Moreover, modifications, including DNA methylation histone involved H19-associated conclusion, via chemoresistance, highlighting promising research significance therapeutic target. We hope our study will contribute broader understanding development treatment.

Language: Английский

Citations

11
LncRNA MIR181A1HG Deficiency Attenuates Vascular Inflammation and Atherosclerosis DOI
Huaner Ni, Yulong Ge, Ying Zhuge

et al.

Circulation Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Endothelial cell (EC) dysfunction and vascular inflammation are critical in the initiation progression of atherosclerosis. Long noncoding RNAs play a role pathology, but relatively little is known about their involvement controlling inflammation. MIR181A1HG conserved long RNA located juxtaposition with miR-181a1 miR-181b1, both involved The study aims to investigate regulating We examined expression human mouse atherosclerotic lesions. Loss-of-function gain-of-function studies, multiple RNA-protein interaction assays were used molecular mechanisms phenotypes MIR181A1HG-/-ApoE-/- mice analyzed combination single-cell sequencing. transcriptional regulation was verified through luciferase reporter chromatin immunoprecipitation assays. abundant ECs significantly increased had reduced NLRP (NLR family pyrin domain containing) 3 inflammasome signaling, EC activation, monocyte infiltration, lesion formation. Genetic deletion myeloid sells did not alter Single-cell sequencing analysis revealed that deficiency proportion immune cells enriched anti-inflammation pathways clusters In contrast, EC-specific overexpression promoted NLRP3 formation, effects reversed by pharmacological inhibition (MCC950). transcriptionally activated via an NF-κB (nuclear factor kappa B)/p65-dependent pathway. Mechanistically, mediated these on activation part decoying Foxp1 (forkhead box transcription 1) away from promoters target genes, which independent miR-181a1/b1 cluster. Finally, silencing antiatherosclerotic effect MIR181A1HG-deletion vivo. These findings identify as central driver atherosclerosis its ability decoy gene activate endothelium. Our suggests future therapeutic for inflammatory disease states.

Language: Английский

Citations

1
Role of lncRNAs in aging and age‐related diseases DOI Creative Commons
Jieyu He, Chao Tu, You‐Shuo Liu

et al.

Aging Medicine, Journal Year: 2018, Volume and Issue: 1(2), P. 158 - 175

Published: July 30, 2018

Abstract Aging is progressive physiological degeneration and consequently declined function, which linked to senescence on both cellular organ levels. Accumulating studies indicate that long noncoding RNA s (lnc s) play important roles in at all levels—transcriptional, post‐transcriptional, translational, post‐translational. Understanding the molecular mechanism of lnc underlying could facilitate interpretation intervention aging age‐related diseases. In this review, we describe categories known novel have been involved progression senescence. We also identify implicated diseases arising from age‐driven or dysfunction some representative organs systems (brains, liver, muscle, cardiovascular system, bone pancreatic islets, immune system). Improved comprehension process levels, cell organismal, may provide new insights into amelioration pathologies prolonged healthspan.

Language: Английский

Citations

77
LncRNA Meg3 protects endothelial function by regulating the DNA damage response DOI Creative Commons
Mohamed Sham Shihabudeen Haider Ali,

Xiao Cheng,

Matthew Moran

et al.

Nucleic Acids Research, Journal Year: 2018, Volume and Issue: 47(3), P. 1505 - 1522

Published: Nov. 15, 2018

The role of long non-coding RNAs (lncRNAs) in regulating endothelial function through the DNA damage response (DDR) remains poorly understood. In this study, we demonstrate that lncRNA maternally expressed gene 3 (Meg3) interacts with RNA binding protein polypyrimidine tract (PTBP3) to regulate expression and p53 signaling ─ a major coordinator apoptosis cell proliferation triggered by DDR. Meg3 is induced cells (ECs) upon activation. silencing induces damage, activates signaling, increases target genes, promotes EC apoptosis, inhibits proliferation. Mechanistically, reduces interaction Mdm2, expression, association promoters subset genes. PTBP3 recapitulates effects deficiency on Meg3-dependent genes suggests restrain Our studies reveal novel function, which may serve as targets for therapies restore homeostasis.

Language: Английский

Citations

77
Regulation of DNA Double-Strand Break Repair by Non-Coding RNAs DOI Creative Commons
Roopa Thapar

Molecules, Journal Year: 2018, Volume and Issue: 23(11), P. 2789 - 2789

Published: Oct. 27, 2018

DNA double-strand breaks (DSBs) are deleterious lesions that generated in response to ionizing radiation or replication fork collapse can lead genomic instability and cancer. Eukaryotes have evolved two major pathways, namely homologous recombination (HR) non-homologous end joining (NHEJ) repair DSBs. Whereas the roles of protein-DNA interactions HR NHEJ been fairly well defined, functions small long non-coding RNAs RNA-DNA hybrids damage is just beginning be elucidated. This review summarizes recent discoveries on identification RNA-mediated regulation DSB repair.

Language: Английский

Citations

74
lncRNA GAS5 promotes M1 macrophage polarization via miR‐455‐5p/SOCS3 pathway in childhood pneumonia DOI

Xiaowen Chi,

Beichen Ding, Lijuan Zhang

et al.

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(8), P. 13242 - 13251

Published: Dec. 24, 2018

We herein aimed to explore whether growth arrest-specific 5 (GAS5) promotes M1 macrophage polarization in childhood pneumonia and investigate the underlying mechanism.Relative GAS5 miR-455-5p expression suppressor of cytokine signaling 3 (SOCS3) messenger RNA level were examined using quantitative reverse transcription polymerase chain reaction. Protein SOCS3 Janus kinase 2/signal transducer activator (JAK2/STAT3) pathway-related proteins was detected western blot analysis. Luciferase activity assay performed test could bind or SOCS3. The phenotype determined flow cytometry analysis enzyme-linked immunosorbent assay.The toward M2 observed peripheral blood from children. Furthermore, upregulated but downregulated human monocyte-derived macrophages children compared with control group. acted as a sponge for facilitate expression. Moreover, mimic knockdown significantly reversed overexpression-mediated suppression JAK2/STAT3 promotion polarization.GAS5 by acting competing endogenous pneumonia.

Language: Английский

Citations

70
MicroRNA-mediated autophagy regulation in cancer therapy: The role in chemoresistance/chemosensitivity DOI
Milad Ashrafizadeh, Ali Zarrabi,

Sima Orouei

et al.

European Journal of Pharmacology, Journal Year: 2020, Volume and Issue: 892, P. 173660 - 173660

Published: Oct. 24, 2020

Language: Английский

Citations

69