The novel regulatory role of lncRNA‐miRNA‐mRNA axis in cardiovascular diseases

Journal of Cellular and Molecular Medicine, Journal Year: 2018, Volume and Issue: 22(12), P. 5768 - 5775

Published: Sept. 6, 2018

Long noncoding RNAs (lncRNAs) are longer than 200 nt in length that characterized by low levels of sequence conservation and expression; lncRNAs modulate various biological functions at epigenetic, transcriptional post-transcriptional levels, or directly regulate protein activity. As a family small evolutionarily conserved RNAs, microRNAs (miRNAs) capable regulating physiological pathological processes via inhibiting target mRNA translation promoting degradation. A number studies have confirmed both miRNAs closely associated with the development cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure, myocardial injury arrhythmia, they act biomarkers, potential therapeutic targets strong indicators prognosis; however, underlying molecular mechanism has not been elucidated. Recently, emerging evidence showed novel regulatory crosstalk among lncRNAs, mRNAs plays pivotal role pathophysiological CVDs response to stress stimuli. In this review, I comprehensively summarized relationship highlighted important lncRNA-miRNA-mRNA axis CVDs.

Language: Английский

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Exosomal lncRNA TUG1 from cancer-associated fibroblasts promotes liver cancer cell migration, invasion, and glycolysis by regulating the miR-524-5p/SIX1 axis

Cellular & Molecular Biology Letters, Journal Year: 2022, Volume and Issue: 27(1)

Published: Feb. 22, 2022

Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized.The expression levels of TUG1, miR-524-5p, sine oculis homeobox homolog (SIX1) were determined using quantitative real-time PCR. The regulatory relationships confirmed by dual-luciferase reporter assay. Cell proliferation invasion assessed Counting Kit 8 transwell assays. Glucose uptake, cellular lactate, lactate dehydrogenase (LDH), adenosine triphosphate (ATP) detected commercially available kits. Silencing TUG1 or SIX1 was performed lentivirus transduction. Protein measured immunoblotting.Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, glycolysis HepG2 cells releasing TUG1. promotive effects CAFs-secreted attenuated silencing targets miR-524-5p. knockdown inhibited miR-524-5p inhibitor. suppressed growth lung metastasis therefore increased survival xenograft model mice. We also found HCC patients with while decreased metastasis.CAFs-derived exosomal via miR-524-5p/SIX1 axis. These findings may help establish foundation development therapeutics strategies clinical management future.

Language: Английский

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The role of PI3K/AKT signaling pathway in myocardial ischemia-reperfusion injury

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 123, P. 110714 - 110714

Published: July 29, 2023

Language: Английский

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Targeting PI3K/Akt in Cerebral Ischemia Reperfusion Injury Alleviation: From Signaling Networks to Targeted Therapy

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(10), P. 7930 - 7949

Published: March 5, 2024

Language: Английский

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Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Sept. 8, 2020

Abstract Drug resistance is a major hurdle in cancer treatment and key cause of poor prognosis. Epitranscriptomics epiproteomics are crucial cell proliferation, migration, invasion, epithelial–mesenchymal transition. In recent years, epitranscriptomic epiproteomic modification has been investigated on their roles overcoming drug resistance. this review article, we summarized the progress three novel aspects: (i) mRNA modification, which includes alternative splicing, A-to-I methylation; (ii) noncoding RNAs involves miRNAs, lncRNAs, circRNAs; (iii) posttranslational molecules encompasses inactivation/efflux, target modifications, DNA damage repair, death resistance, EMT, metastasis. addition, discussed therapeutic implications targeting some classical chemotherapeutic drugs such as cisplatin, 5-fluorouridine, gefitinib via these modifications. Taken together, highlights importance provides new insights potential targets to reverse

Language: Английский

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From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases

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

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TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: March 24, 2022

Chronic kidney disease (CKD) was a major public health problem worldwide. Renal fibrosis, especially tubulointerstitial is final manifestation of CKD. Many studies have demonstrated that TGF-β/Smad signaling pathway plays crucial role in renal fibrosis. Therefore, targeted inhibition can be used as potential therapeutic measure for At present, variety targeting TGF-β1 and its downstream Smad proteins attracted attention. Natural products strategies fibrosis the characteristics acting on multiple targets by components few side effects. With continuous research technique development, more molecular mechanisms natural been revealed, there are many inhibited via pathway. This review summarized against Additionally, challenges opportunities presented inhibiting future.

Language: Английский

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Exosomal lncRNA HOTAIR Promotes the Progression and Angiogenesis of Endometriosis via the miR-761/HDAC1 Axis and Activation of STAT3-Mediated Inflammation

International Journal of Nanomedicine, Journal Year: 2022, Volume and Issue: Volume 17, P. 1155 - 1170

Published: March 1, 2022

Background: Long non-coding RNA (lncRNA) and exosomes are implicated in endometriosis development. We measured the expression of an exosomal lncRNA, homeobox transcript antisense (HOTAIR), explored its molecular mechanism progression. Methods: Expression HOTAIR microRNA (miR)-761 different endometrial tissues was measured. Exosomes were isolated from a culture medium stromal cells (ESCs). RT-qPCR used to measure exosome types. CCK-8, Edu, wound healing, transwell assays, flow cytometry tube formation detect role on ESCs human umbilical vein endothelial (HUVECs). The relationship among miR-761, HOTAIR, histone deacetylase 1 (HDAC1) verified by dual-luciferase reporter assay. transfected with miR-761 mimics or HDAC1 small interfering (si-RNA) ascertain if alterations could reverse effect HOTAIR. Then, we detected HOTAIR/miR-761/HDAC1 axis signal transducer activator transcription 3 (STAT3)-mediated inflammation. In vivo experiments conducted verify vitro results. Results: upregulated downregulated ectopic endometrium tissues. packaged into transported surrounding cells. Exosomal promoted proliferation, migration, invasion, inhibited apoptosis ESCs. Angiogenesis HUVECs enhanced after cultured acted as competing endogenous downregulate increase expression. overexpression knockdown reversed HUVECs. activate STAT3-related proinflammatory cytokines stattic (inhibitor phosphorylated-STAT3) suggested that growth lesions vivo. Conclusion: progression angiogenesis regulating miR-761/HDAC1 activating STAT3-mediated inflammation vivo, which may provide promising treatment for endometriosis. Keywords: endometriosis, exosomes, HDAC1, STAT3,

Language: Английский

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Insulin-like growth factor 2 mRNA-binding protein 2-stabilized long non-coding RNA Taurine up-regulated gene 1 (TUG1) promotes cisplatin-resistance of colorectal cancer via modulating autophagy

Bioengineered, Journal Year: 2022, Volume and Issue: 13(2), P. 2450 - 2469

Published: Jan. 11, 2022

Long non-coding RNAs (lncRNAs) have been demonstrated to influence the chemoresistance of colorectal cancer (CRC). Therefore, study is designed investigate regulatory function and mechanism Taurine up-regulated gene 1 (TUG1) in cisplatin resistance CRC. qRT-PCR checked expressions TUG1, Insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), miR-195-5p CRC tissues cells. The TUG1 or overexpression model was engineered cells, followed by treatment with DDP autophagy inhibitor (Chloroquine, CQ). CCK8 (Cell Counting Kit-8) colony formation experiment monitored cell proliferation. Flow cytometry examined apoptosis, Transwell tracked migration invasion, Western blot ascertained profiles proteins (LC3I/LC3II Beclin1) HDGF/DDX5/β-catenin pathway. Dual-luciferase reporter assay RNA immunoprecipitation confirmed binding correlation between HDGF. Furthermore, in-vivo experiments nude mice probed IGF2BP2 growth. were elevated tissues, enhanced TUG1's expression activated facilitate cells' DDP. targets miR-195-5p, Overexpression abated cancer-promoting curbed profile axis. stabilized boosted proliferation, migration, via miR-195-5p/HDGF/DDX5/β-catenin axis, hence enhancing cell's

Language: Английский

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Navigating the landscape of RNA delivery systems in cardiovascular disease therapeutics

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 208, P. 115302 - 115302

Published: April 3, 2024

Cardiovascular diseases (CVDs) stand as the leading cause of death worldwide, posing a significant global health challenge. Consequently, development innovative therapeutic strategies to enhance CVDs treatment is imperative. RNA-based therapies, encompassing non-coding RNAs, mRNA, aptamers, and CRISPR/Cas9 technology, have emerged promising tools for addressing CVDs. However, inherent challenges associated with RNA, such poor cellular uptake, susceptibility RNase degradation, capture by reticuloendothelial system, underscore necessity combining these therapies effective drug delivery systems. Various non-viral systems, including extracellular vesicles, lipid-based carriers, polymeric inorganic nanoparticles, well hydrogels, shown promise in enhancing efficacy RNA therapeutics. In this review, we offer an overview most relevant explored emphasize pivotal role systems augmenting their effectiveness. Additionally, discuss current status that hinder clinical translation.

Language: Английский

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