Hsa_circ_0125356 promotes gemcitabine resistance by modulating WNT canonical and non-canonical pathways via miR-582-5p/FGF9 axis in non-small cell lung cancer

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 27, 2025

Non-small cell lung cancer (NSCLC) is the leading cause of morbidity and mortality worldwide. The prognosis patients has been significantly improved by chemotherapy, but acquired drug resistance remains a major obstacle to NSCLC treatment. Circular RNAs (circRNAs), which act as miRNA or protein sponges, are critically associated with development chemotherapy NSCLC. CircRNA sequencing was performed analyze differential expression circRNAs between A549 A549-GR cells. Chromogenic in situ hybridization (CISH) immunohistochemistry (IHC) technologies were used detect hsa_circ_0125356, miR-582-5p,and FGF9 tissues para-carcinoma tissues. Fluorescence (FISH), dual-luciferase reporter assays RNA immunoprecipitation (RIP) conducted evaluate regulation miR-582-5p, FGF9. Furthermore, hsa_circ_0125356/miR-582-5p/FGF9 on gemcitabine sensitivity confirmed TUNEL, Transwell, EdU, CCK8 immunohistochemistry. We identified novel hsa_circ_0125356 therapeutic target against resistance. Hsa_circ_0125356 elevated clinical samples Moreover, overexpression promoted upregulating via sponging miR-582-5p vivo vitro. Notably, WNT canonical (ERK/GSK3β/β-catenin) non-canonical (Daam1/RhoA/ROCK2) signaling pathways activated due acting an endogenous sponge regulate FGF9, thereby enhancing promoting DNA damage repair inhibition apoptosis. results further two small molecule antagonists, WAY 316606 XAV-939,which could inhibit activation pathway induced hsa_circ_0125356. first demonstrated that upregulated served biomarker for miR-582-5p/FGF9 axis pathways, provided new direction identification targets treatment

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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Advances in understanding the role of squalene epoxidase in cancer prognosis and resistance

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Jan. 27, 2025

Language: Английский

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Proteomics of stress-induced cardiomyopathy: insights from differential expression, protein interaction networks, and functional pathway enrichment in an isoproterenol-induced TTC mouse model

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e18984 - e18984

Published: Feb. 13, 2025

Backgrounds Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, is a condition characterized by transient left ventricular dysfunction without coronary artery obstruction. Methods We utilized label-free quantitative proteomics to analyze protein expression in murine model of TTC, induced high dose isoproterenol (ISO) injection. Results found that single ISO injection mice could induce stress-related cardiac dysfunction.The proteomic analysis revealed 81 differentially expressed proteins (DEPs) between the and control groups—39 were upregulated, 42 downregulated. Key pathways enriched Gene Ontology (GO) included collagen fibril organization, cholesterol biosynthesis, elastic fiber assembly. Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment indicated significant changes unsaturated fatty acid glutathione metabolism, steroid ferroptosis. hub identified protein-protein interaction (PPI) network Ntrk2, Fdft1, Serpine1, Cyp1a1. set (GSEA) showed upregulation terpenoid backbone oxidative phosphorylation, ferroptosis, with downregulation such systemic lupus erythematosus Rap1 signaling. Conclusions This study employed high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) identify key associated energy stress, inflammation, cell death TTC. These findings provide new insights into molecular mechanisms myocardial injury may offer potential therapeutic targets for mitigating cardiovascular damage under stress conditions.

Language: Английский

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Squalene Epoxidase: Its Regulations and Links with Cancers

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3874 - 3874

Published: March 30, 2024

Squalene epoxidase (SQLE) is a key enzyme in the mevalonate–cholesterol pathway that plays critical role cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes first oxygenation step pathway. Recently, intensive efforts have been made extend current knowledge of SQLE cancers through functional mechanistic studies. However, underlying mechanisms not fully elucidated yet. In this review, we retrospected as rate-limiting pathway, while shedding light on its potential diagnostic prognostic marker, revealed therapeutic values cancers. We showed regulated at different levels involved crosstalk with iron-dependent cell death. Particularly, systemically reviewed research findings Finally, discussed implications inhibitors summarized their clinical values. Overall, review multifaceted involve present vivid panorama

Language: Английский

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Transcriptomic and epigenomic landscapes of muscle growth during the postnatal period of broilers

Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 4, 2024

Broilers stand out as one of the fastest-growing livestock globally, making a substantial contribution to animal meat production. However, molecular and epigenetic mechanisms underlying rapid growth development broiler chickens are still unclear. This study aims explore muscle patterns regulatory networks during postnatal phase fast-growing broilers. We measured performance Cornish (CC) White Plymouth Rock (RR) over 42-d period. Pectoral samples from both CC RR were randomly collected at day 21 after hatching (D21) D42 for RNA-seq ATAC-seq library construction. The consistent increase in body weight pectoral across breeds was observed they matured, with outpacing terms each stage development. Differential expression analysis identified 398 1,129 genes two dimensions ages, respectively. A total 75,149 peaks annotated promoter, exon, intron intergenic regions, higher number promoter intronic regions. age-biased breed-biased combined data subsequent analysis. results spotlighted upregulation ACTC1 FDPS D21, which primarily associated structure by gene cluster enrichment. Additionally, noteworthy MUSTN1, FOS TGFB3 spotted D42, involved cell differentiation regeneration injury, suggesting role repair. work provided network revealed MUSTN1 key responsible regeneration. Our findings highlight that triggers ongoing damage These provide foundation future research investigate functional aspects

Language: Английский

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Integrative analysis of miRNAs and proteins in plasma extracellular vesicles of patients with familial hypercholesterolemia

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 568, P. 120123 - 120123

Published: Jan. 7, 2025

Language: Английский

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ASFV infection induces lipid metabolic disturbances and promotes viral replication

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

African swine fever is a highly transmissible and lethal infectious disease caused by the virus (ASFV), which has considerably impacted global industry. Lipid metabolism plays vital role in sustaining lipid energy homeostasis within cells influences viral life cycle. In this study, we found that ASFV infection disrupts host. Transcriptomic analysis of infected with revealed levels significantly changed as duration progressed. The intracellular cholesterol host exhibited pattern similar to growth curve during course infection. Notably, increased promoted replication cells, whereas inhibition biosynthesis pathway markedly reduced replication. findings study showed led disturbances facilitate its replication, useful for revealing mechanism underlying

Language: Английский

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Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 14, 2025

Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria lysosomes, independent of mitophagy the lysosomal degradation mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk these cell compartments, regulation organelle networks, substance exchanges. Emerging evidence suggests that abnormalities mitochondria-lysosome (MLCSs) contribute to diseases, including Parkinson’s disease, Charcot–Marie-Tooth (CMT) storage epilepsy. This article reviews recent research advances regarding tethering processes, regulation, function MLCSs role

Language: Английский

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Reading through circular RNAs in MASLD: new diagnostic and therapeutic opportunities may come around

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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