SQLE, A Key Enzyme in Cholesterol Metabolism, Correlates With Tumor Immune Infiltration and Immunotherapy Outcome of Pancreatic Adenocarcinoma

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

Published: May 26, 2022

Pancreatic adenocarcinoma (PAAD) is a treatment-refractory cancer with poor prognosis. Accumulating evidence suggests that squalene epoxidase (SQLE) plays pivotal role in the development and progression of several types humans. However, function underlying mechanism SQLE PAAD remain unclear.SQLE expression data were downloaded from The Cancer Genome Atlas Genotype-Tissue Expression database. alterations demonstrated based on cBioPortal upstream miRNAs regulating predicted using starBase. miRNA was validated by Western blotting cell proliferation assay. relationship between biomarkers tumor immune microenvironment (TME) analyzed TIMER TISIDB databases. correlation immunotherapy outcomes assessed Tumor Immune Dysfunction Exclusion. log-rank test performed to compare prognosis high low groups.We potential oncogenic SQLE. upregulated PAAD, it disease-free survival (DFS) overall (OS) patients PAAD. "Amplification" dominant type alteration. In addition, this alteration closely associated OS, disease-specific survival, DFS, progression-free Subsequently, hsa-miR-363-3p recognized as critical microRNA thereby influencing patient outcome. vitro experiments suggested miR-363-3p could knock down inhibit PANC-1. significantly infiltration, checkpoints (including PD-1 CTLA-4), TME. KEGG GO analyses indicated cholesterol metabolism-associated RNA functions are implicated mechanisms inversely cytotoxic lymphocytes outcomes.Collectively, our results indicate metabolism-related overexpression strongly correlated infiltration

Language: Английский

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Role of non-coding RNAs in tumor progression and metastasis in pancreatic cancer

Cancer and Metastasis Reviews, Journal Year: 2021, Volume and Issue: 40(3), P. 761 - 776

Published: Sept. 1, 2021

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types cancer with an overall 5-year survival rate less than 10%. The 1-year patients locally advanced or metastatic disease abysmal. aggressive nature cells, hypovascularization, extensive desmoplastic stroma, and immunosuppressive tumor microenvironment (TME) endows PDAC tumors multiple mechanisms drug resistance. With no obvious genetic mutation(s) driving progression transition, challenges for understanding biological mechanism(s) these processes are paramount. A better molecular cellular could lead to new diagnostic tools patient management targets therapeutic intervention. microRNAs (miRNAs) evolutionarily conserved gene class short non-coding regulatory RNAs. miRNAs layer that controls expression at posttranscriptional level. This review focuses on preclinical models functionally dissect miRNA activity in PDAC. Collectively, studies suggest influence RNA-RNA networks epithelial mesenchymal cell transition stemness. At a cell-type level, some mainly cell–intrinsic pathways, whereas other predominantly act distinct compartments TME regulate fibroblast immune functions and/or types’ function via cell-to-cell communications by transfer extracellular vesicles. miRNA-mediated regulation often converges core signaling including TGF-β, JAK/STAT, PI3K/AKT, NF-κB.

Language: Английский

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Deciphering the Biological Effects of Radiotherapy in Cancer Cells

Biomolecules, Journal Year: 2022, Volume and Issue: 12(9), P. 1167 - 1167

Published: Aug. 23, 2022

Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy radiotherapy is compromised by development radioresistance tumor cells during treatment. Consequently, there need a comprehensive understanding regulatory mechanisms in response to radiation improve efficacy. The current study aims highlight new developments that illustrate various forms cancer cell death after exposure radiation. A summary cellular pathways and important target proteins are responsible metastasis also provided. Further, outlines several mechanistic descriptions interaction between ionizing host immune system. Therefore, review provides reference future research studies on biological effects technologies, such as ultra-high-dose-rate (FLASH) radiotherapy, proton therapy, heavy-ion therapy.

Language: Английский

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The emerging role of exosomes in radiotherapy

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Oct. 31, 2022

Abstract Presently, more than half of cancer patients receive radiotherapy to cure localized cancer, palliate symptoms, or control the progression cancer. However, radioresistance and radiation-induced bystander effects (RIBEs) are still challenging problems in treatment. Exosomes, as a kind extracellular vesicle, have significant function mediating regulating intercellular signaling pathways. An increasing number studies shown that can increase exosome secretion alter cargo. Furthermore, exosomes involved mechanism RIBEs. Therefore, hold great promise for clinical application radiotherapy. In this review, we not only focus on influence radiation biogenesis, cargoes but also RIBEs, which may expand our insight into cooperative

Language: Английский

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Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 16, 2024

Adipose tissue (AT) serves as an energy-capacitive organ and performs functions involving paracrine- endocrine-mediated regulation via extracellular vesicles (EVs) secretion. Exosomes, a subtype of EVs, contain various bioactive molecules with regulatory effects, such nucleic acids, proteins, lipids. AT-derived exosomes (AT-exos) include derived from cells in AT, including adipocytes, adipose-derived stem (ADSCs), macrophages, endothelial cells. This review aimed to comprehensively evaluate the impacts different AT-exos on physiological pathological processes. The contents adipocyte-derived ADSC-derived are compared simultaneously, highlighting their similarities differences. have been shown exert complex effects local inflammation, tumor dynamics, insulin resistance. Significantly, differences cargoes observed among diabetes patients, obese individuals, healthy individuals. These could be used predict development mellitus therapeutic targets for improving sensitivity glucose tolerance. However, further research is needed elucidate underlying mechanisms potential applications AT-exos.

Language: Английский

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