Exosomal circSHKBP1 promotes gastric cancer progression via regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: June 29, 2020

Abstract Background Circular RNAs (circRNAs) play important regulatory roles in the development of various cancers. However, biological functions and underlying molecular mechanism circRNAs gastric cancer (GC) remain obscure. Methods Differentially expressed were identified by RNA sequencing. The circSHKBP1 GC investigated a series vitro vivo experiments. expression was evaluated using quantitative real-time PCR situ hybridization, demonstrated western blot, pulldown, immunoprecipitation, luciferase assays rescue Lastly, mouse xenograft bioluminescence imaging used to exam clinical relevance vivo. Results Increased circSHKBP1(hsa_circ_0000936) revealed tissues serum related advanced TNM stage poor survival. level exosomal significantly decreased after gastrectomy. Overexpression promoted cell proliferation, migration, invasion angiogenesis vivo, while suppression plays opposite role. Exosomes with upregulated cocultured cells growth. Mechanistically, sponged miR-582-3p increase HUR expression, enhancing VEGF mRNA stability. Moreover, directly bound HSP90 obstructed interaction STUB1 HSP90, inhibiting ubiquitination resulting accelerated Conclusion Our findings demonstrate that regulates miR-582-3p/HUR/VEGF pathway, suppresses degradation, promotes progression. is promising circulating biomarker for diagnosis prognosis an exceptional candidate further therapeutic exploration.

Language: Английский

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Epigenetic regulation of aging: implications for interventions of aging and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 7, 2022

Abstract Aging is accompanied by the decline of organismal functions and a series prominent hallmarks, including genetic epigenetic alterations. These aging-associated changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, all which participate in regulation aging process, hence contribute to aging-related diseases. Therefore, understanding mechanisms will provide new avenues develop strategies delay aging. Indeed, interventions based on manipulating have led alleviation or extension lifespan animal models. Small molecule-based therapies reprogramming that enable rejuvenation been developed for ameliorating reversing conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, calibrating circadian rhythm, has demonstrated Furthermore, various clinical trials intervention are ongoing, providing more evidence safety efficacy these therapies. Here, we review recent work outline advances age-associated A better critical roles epigenetics process lead prevention human therapy

Language: Английский

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Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: Jan. 23, 2020

Exosomes play crucial roles in regulating the crosstalk between normal and cancer cells tumor microenvironment, proliferation, migration invasion through their cargo molecules. We analyzed pro-invasiveness of exosomal circRNA-100,338 HCC using transwell assay. The co-culture human umbilical vein endothelial (HUVEC) exosomes derived from cell lines were used to evaluate impact on HUVEC. Nude mice models validate findings vitro. Clinically, quantitative RT-PCR was quantify expression serum patients at both pre-surgery within one week post-surgery three weeks. aim investigate pro-invasive role metastasis. for first time demonstrated that highly expressed metastatic secreted exosomes. assay showed overexpression or knockdown significantly enhanced reduced invasive abilities cells. Subsequently, vitro vivo assays affected angiogenesis, permeability, vasculogenic mimicry (VM) formation ability (HUVEC), Furthermore, we also observed persistent high who underwent curative hepatectomy may be a risk indicator pulmonary metastasis poor survival. Our indicated could by transferring recipient HUVECs, which affect proangiogenic activity angiogenesis.

Language: Английский

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Mitophagy in degenerative joint diseases

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2082 - 2092

Published: Sept. 24, 2020

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis function important. Mitophagy, a process that selectively clears damaged or dysfunctional through autophagic machinery, functions to maintain mitochondrial quality control homeostasis. IVDD OA are similar joint diseases involving degradation cartilaginous tissues mainly caused by oxidative stress, cell apoptosis extracellular matrix (ECM) degradation. Over past decade, accumulating evidence indicates essential role mitophagy pathogenesis OA. Importantly, strategies regulation exert beneficial effects pre-clinical experiments. Given importance novelty mitophagy, we provide an overview pathways discuss roles We also highlight potential targeting for treatment diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B 3-like; CDH6: cadherin 6; CEP: endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin beta; IMM: inner membranes; IVDD: degeneration; MAPK8/JNK: mitogen-activated kinase 8; MFN1: mitofusin MFN2: 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: transmembrane potential; CALCOCO2/NDP52: calcium binding coiled-coil domain NFE2L2: nuclear factor: erythroid 2 like NP: nucleus pulposus; OA: osteoarthritis; OPA1: GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin ligase; PD: Parkinson PGAM5: PGAM 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator alpha; PHF23: PHD finger 23; PINK1: PTEN induced putative ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin SIRT2: SIRT3: SQSTM1/p62: sequestosome TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

Language: Английский

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The bioinformatics toolbox for circRNA discovery and analysis

Briefings in Bioinformatics, Journal Year: 2020, Volume and Issue: 22(2), P. 1706 - 1728

Published: Jan. 2, 2020

Circular RNAs (circRNAs) are a unique class of RNA molecule identified more than 40 years ago which produced by covalent linkage via back-splicing linear RNA. Recent advances in sequencing technologies and bioinformatics tools have led directly to an ever-expanding field types biological functions circRNAs. In parallel with technological developments, practical applications circRNAs arisen including their utilization as biomarkers human disease. Currently, circRNA-associated can support projects circRNA annotation, identification network analysis competing endogenous (ceRNA). this review, we collected about 100 summarized current attributes capabilities. We also performed text mining on tool publications order reveal trends ongoing development.

Language: Английский

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