Identification of cancer cell-intrinsic biomarkers associated with tumor progression and characterization of SFTA3 as a tumor suppressor in lung adenocarcinomas

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 8, 2025

Recent advancements in contemporary therapeutic approaches have increased the survival rates of lung cancer patients; however, long-term benefits remain constrained, underscoring pressing need for novel biomarkers. Surfactant-associated 3 (SFTA3), a long non-coding RNA predominantly expressed normal epithelial cells, plays crucial role development. Nevertheless, its function adenocarcinoma (LUAD) remains inadequately understood. Single-cell sequencing data were utilized to identify cell-intrinsic gene signatures associated with progression LUAD, and their roles LUAD comprehensively analyzed. Serum samples collected quantify expression levels SFTA3 patients. Furthermore, series biological experiments, including cell viability assays, scratch wound healing colony formation conducted demonstrate tumor-suppressive effects SFTA3. was performed elucidate molecular mechanisms underlying cells. We constructed prognostic model comprising eight genes: ALDOA, ATP5MD, SERPINH1, SFTA3, SLK, U2SURP, SCGB1A1, SCGB1A3. The effectively stratified patients into high- low-risk categories, revealing that experienced superior clinical outcomes, exhibited an immunologically hot tumor microenvironment (TME), had greater probability responding immunotherapy. In contrast, high-risk group cold TME may benefit more from chemotherapy. our study revealed progressive decrease cells correlated advancement. Notably, serum significantly decreased suggesting potential utility liquid biopsy diagnosis. Additionally, knockdown enhances proliferation migration whereas overexpression inhibits these phenotypes. epithelial-mesenchymal transition pathway enriched following silencing, impact by modulating this process. also identified key transcription factors epigenetic implicated downregulation LUAD. developed robust as biomarker applications diagnosis, prognosis, personalized treatment findings offer new insights tumorigenesis immune evasion.

Язык: Английский

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Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases

Biomolecules, Год журнала: 2025, Номер 15(1), С. 121 - 121

Опубликована: Янв. 14, 2025

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack clinically validated early-stage biomarkers limited availability effective anti-fibrotic therapies. Current research focused on uncovering pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic diseases, such as inflammation, hepatic stellate cell activation proliferation, extracellular matrix production, are being developed. Etiology-specific treatments, those for hepatitis B C viruses, already clinical use, efforts develop new, targeted therapies other diseases ongoing. In this review, we highlight major changes occurring patients affected metabolic dysfunction-associated steatotic disease, viral (Delta virus), autoimmune (autoimmune hepatitis, primary biliary cholangitis, sclerosing cholangitis). Further, describe how knowledge linked current well ongoing preclinical novel strategies, including nucleic acid-, mesenchymal stromal/stem cell-, vesicle-based options. Much development obviously still missing, but plethora promising potential treatment strategies holds promise future reversal increase group patients.

Язык: Английский

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Exploring the Potential of tsRNA as Biomarkers for Diagnosis and Treatment of Neurogenetic Disorders

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Язык: Английский

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Extracellular vesicles derived microRNAs as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study

Non-coding RNA Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis (CHC) progression. The objective of study was to delve into intricate EVs-miRNA profiles CHC patients different fibrosis stages, aiming pinpoint non-invasive markers capable distinguishing significant fibrosis. Plasma EV-miRNAs from 50 (HCV+ and HCV+/HIV+) stratified no (F < 2) ≥ fibrosis, were massively sequenced. General linear models (GLM) used identify differential expressed (SDE) miRNAs according stages 2 F 2). Dysregulated biological pathways subsequently analyzed silico following groups: i) all patients; ii) HCV+; iii) HCV+/HIV+. Multiple-ordered logistic regression analysis performed develop a score cases. diagnostic potential both SDE developed assessed using ROC curve analysis. With respect patients, two (hsa-miR-122-5p hsa-miR-92a-3p) identified which regulate genes related cytoskeleton organization. Regarding their performance discriminate 2, individually demonstrated acceptable values. However, combined use new enhanced (AUROC = 0.833). In HCV+ subgroup, 8 (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), macrophage activity cell growth/death regulation, recognized. Among them, hsa-miR-3615 displayed highest 0.936). HCV+/HIV+, 18 (hsa-miR-4508, hsa-miR-122-5p, hsa-miR-451a, hsa-miR-1290, hsa-miR-1246, hsa-miR-107, hsa-miR-15b-5p, hsa-miR-194-5p, hsa-miR-22-5p, hsa-miR-20b-5p, hsa-miR-142-5p, hsa-miR-328-3p, hsa-miR-335-3p, hsa-miR-125a-5p, hsa-miR-423-3p, hsa-let-7d-3p, hsa-miR-128-3p, hsa-miR-10a-5p) recognized that RNA silencing processes. this case, hsa-miR-423-3p hsa-miR-128-3p showed outstanding performances > 0.900). Distinct varying overall cohort within HCV+/HIV+ subgroups. These specific miRNA signatures would allow elucidation mechanisms involved clinical evolution identification biomarkers unfavorable progression, plausible be panel. Furthermore, demonstrates ability group those individuals regardless HIV status.

Язык: Английский

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Electrochemical Biosensors for the Detection of Exosomal microRNA Biomarkers for Early Diagnosis of Neurodegenerative Diseases

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 9, 2025

Early and precise diagnosis of neurodegenerative disorders like Alzheimer's (AD) Parkinson's (PD) is crucial for slowing their progression enhancing patient outcomes. Exosomal microRNAs (miRNAs) are emerging as promising biomarkers due to ability reflect the diseases' pathology, yet low abundance poses significant detection hurdles. This review article delves into burgeoning field electrochemical biosensors, designed exosomal miRNA biomarkers. Electrochemical biosensors offer a compelling solution, combining sensitivity required detect low-abundance with specificity needed discern profiles distinctive neural pathological states. We explore operational principles these including transduction mechanisms that facilitate detection. The also summarizes advancements in nanotechnology, signal enhancement, bioreceptor anchoring, microfluidic integration improve sensor accuracy. evidence use disease analyzed, focusing on clinical impact, diagnostic precision, obstacles faced practical applications. Their potential point-of-care testing regulatory considerations market entry discussed. Looking toward future, highlights forthcoming innovations might revolutionize early processes. impressive sensitivity, specificity, compatibility, track become instrumental diseases, possibly transforming care prognosis.

Язык: Английский

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RNA-binding protein transcripts as potential biomarkers for detecting Primary Sclerosing Cholangitis and for predicting its progression to Cholangiocarcinoma

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Июнь 6, 2024

Primary Sclerosing Cholangitis (PSC) is a persistent inflammatory liver condition that affects the bile ducts and commonly diagnosed in young individuals. Despite efforts to incorporate various clinical, biochemical molecular parameters for diagnosing PSC, it remains challenging, no biomarkers characteristic of disease have been identified hitherto. PSC linked with an uncertain prognosis, there pressing need explore multiomics databases establish new biomarker panel early detection PSC’s gradual progression into Cholangiocarcinoma (CCA) development effective therapeutic interventions. Apart from non-coding RNAs, other components Ribonucleoprotein (RNP) complex, such as RNA-Binding Proteins (RBPs), also hold great promise due their versatile expression pathological conditions. In present review, update on RBP transcripts show dysregulated CCA provided. Moreover, by utilizing bioinformatic data mining approach, we give insight those exhibit differential gall bladder, well body fluids, are promising predicting prognosis PSC. Expression were bioinformatically extracted public repositories usingTCGA Bile Duct Cancer dataset specific NCBI GEO datasets both CCA; more specifically, RBPs annotations obtained World database. Interestingly, our comprehensive analysis shows elevated non-canonical RBPs, FANCD2 , microtubule dynamics regulator, ASPM fluids patients compared respective controls, same trend being observed bladder cancer tissues. Consequently, manipulation tissue might be considered strategy mitigate onset patients, warrants further experimental investigation. The performed herein may helpful identification non-invasive its CCA. conclusion, future clinical research should investigate depth full potential human pathologies.

Язык: Английский

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Novel insights into the role of immunomodulatory extracellular vesicles in the pathogenesis of liver fibrosis

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 12, 2024

Abstract Liver fibrosis, a chronic and long-term disease, can develop into hepatocellular carcinoma (HCC) ultimately lead to liver failure. Early diagnosis effective treatment still face significant challenges. inflammation leads fibrosis through continuous activation of hepatic stellate cells (HSCs) the accumulation immune cells. Intracellular communication among various is important for mediating inflammatory response during fibrogenesis. Extracellular vesicles (EVs), which are lipid bilayer membrane-enclosed particles naturally secreted by cells, make great contributions cell-cell transport bioactive molecules. Nearly all that participate in release EVs loaded with lipids, proteins, nucleic acids. from hepatocytes, stem involved microenvironment fibrosis. Recently, an increasing number extracellular vesicle-based clinical applications have emerged, providing promising cell-free diagnostic therapeutic tools because their crucial role immunomodulation pathogenesis. The advantages therapies include stability, biocompatibility, low cytotoxicity, minimal immunogenicity, highlight potential drug delivery specific treatments In this review, we summarize complex biological functions pathogenesis evaluate

Язык: Английский

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Expression of miRNAs (146a and 155) in human peri-implant tissue affected by peri-implantitis: a case control study

BMC Oral Health, Год журнала: 2024, Номер 24(1)

Опубликована: Июль 28, 2024

Abstract Background In literature, the levels of miRNA-146a and miRNA-155 are increased in periodontitis. Limited data available regarding expression miR-NA-155 diseased human peri-implant tissue. Therefore, objective this study was to explore gingival tissue affected by peri-implantitis. Methods After recording clinical parameters, pocket tissues were harvested from sites diagnosed with peri-implantitis ( n = 15 cases) addition healthy sulcus controls). The assessed using real-time qPCR. Results Cases exhibited a significantly higher mean (5.2-fold increase) (2.8-fold than controls. MiRNA-155 demonstrated an appropriate sensitivity (87.5% 87.5%, respectively) specificity (73.3% 66.7%, discriminating cases A moderate correlation r 0.544, p 0.029) found between case group. Conclusions expressions different tissues. Both miRNAs might potentially able discriminate

Язык: Английский

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Extracellular Vesicle-Enclosed Oxidative Stress- and Inflammation-Related microRNAs as Potential Biomarkers of Vitamin D Responsivity: A Pilot Study on Inflammatory Bowel Disease Patients with or without COVID-19

Antioxidants, Год журнала: 2024, Номер 13(9), С. 1047 - 1047

Опубликована: Авг. 28, 2024

The relationship between serum 25-hydroxyvitamin D (25(OH)D) levels, genomic response to vitamin (Vit.D), and positivity SARS-CoV-2 remains understudied. In this pilot study, during the follow-up of patients with Inflammatory Bowel Disease (IBD) COVID-19, we investigated issue by analyzing molecular contents extracellular vesicles (EVs) from six groups IBD (n = 32), classified according anti-SARS-CoV-2 status, 25(OH)D level, Vit.D supplementation, small RNA-seq. This analysis revealed differentially expressed miRNAs, PIWI-RNA, transfer RNA, nucleolar RNAs, protein-coding RNAs in EVs obtained these cohorts patients. Experimental validation evidenced a statistically significant increase miR30d-5p, miR150-5p, Let-7f-5p, Let-7a-5p anti-SARS-CoV-2-positive low supplemented respect non-Vit.D group, indicating their responsiveness treatment. Bioinformatics highlighted regulation validated miRNAs oxidative stress inflammation, hallmarks COVID-19. Our study reports an unprecedented panel circulating EV-enclosed inflammation- stress-related potentiality which, as biomarkers for responsivity patients, needs be explored future studies on larger order allow clinicians optimize current treatment strategies upon viral infection.

Язык: Английский

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Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 28, 2024

Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized important non-invasive biomarkers hepatocellular carcinoma (HCC) due presence variety biomolecules within them, such proteins RNAs, etc. play key role early detection, diagnosis, treatment, prognostic monitoring HCC. These influence development HCC therapeutic response ways, including influencing tumor microenvironment, resistance, participating immune regulatory mechanisms. In addition, specific molecules miRNAs are regarded markers for treatment recurrence which certain space prospects. this paper, we summarize aspects markers, also discuss questions that may be faced markers.

Язык: Английский

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