genome-wide-crispr-screen-for-unveiling-radiosensitive-radioresistant

Genome-Wide CRISPR Screen for Unveiling Radiosensitive and Radioresistant Genes

The CRISPR-Cas9 system has been harnessed and repurposed into a powerful genome editing tool. By leveraging this technology, researchers can precisely ...

zhongnan hospital of Wuhan University

Age-related macular degeneration (AMD) is a blinding eye disease, whose incidence strongly increases with ages. The etiology of AMD is complex, including aging, abnormal lipid metabolism, chronic inflammation and oxidative stress. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for ocular structures and functions. This review summarizes the regulatory effects of LCPUFA on inflammation in AMD. LCPUFA are related to aging, autophagy and chronic inflammation. They are metabolized to pro- and anti-inflammatory metabolites by various enzymes. These metabolites stimulate inflammation in response to oxidative stress, causing innate and acquired immune responses. This review also discusses the possible clinical applications, which provided novel targets for the prevention and treatment of AMD and other age-related diseases.

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration.

Long-chain polyunsaturated fatty acids (LCPUFAs) and their metabolites are closely related to neovascular eye diseases. However, the clinical significance of their oxylipins in retinal vein occlusion (RVO) remains inconclusive.

Metabolomic Profiling of Long-Chain Polyunsaturated Fatty Acid Oxidation in Adults with Retinal Vein Occlusion: A Case-Control Study.

The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target for cancer therapy. As a cell adhesion molecule, EpCAM has a crystal structure that indicates that it forms a cis-dimer first and then probably a trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), EpCAM and its proteolytic fragments are also able to regulate multiple signaling pathways, Wnt signaling in particular. Although great progress has been made, increasingly more findings have revealed the context-specific expression and function patterns of EpCAM and their regulation processes, which necessitates further studies to determine the structure, function, and expression of EpCAM under both physiological and pathological conditions, broadening its application in basic and translational cancer research.

Regulation of the Function and Expression of EpCAM.

Anaplastic thyroid carcinoma (ATC) is a highly aggressive human malignancy without effective treatment. Yes-associated protein (YAP) is a critical effector of the Hippo pathway, which is essential in thyroid carcinogenesis. However, the underlying mechanisms of aberrant YAP expression in ATC are not completely understood. Ubiquitylation-related enzyme siRNA screening identified the ubiquitin protein ligase E3 component n-recognin 1 (UBR1) as a stabilizer of YAP in ATC cells. UBR1 deficiency reduced YAP protein levels and its target gene expression. UBR1 directly interacted with YAP and promoted its monoubiquitylation, competitively suppressing its polyubiquitylation and resulting in extended protein half-life. UBR1 depletion reduced ATC cell proliferation and migration in vitro. Xenograft tumor studies also suggested that UBR1 knockdown suppressed ATC cell growth in vivo. Furthermore, exogenous YAP expression partially reversed the inhibitive effects of UBR1 depletion on ATC cell proliferation and migration. Our studies demonstrated that UBR1 directly interacts with YAP and stabilized it in a monoubiquitylation-dependent manner, consequently promoting ATC tumorigenesis, suggesting that UBR1 might be a potentially therapeutic target for ATC treatment.

UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation.

Over the past decades, researchers have continuously investigated the potential functions of long-chain polyunsaturated fatty acids (LCPUFAs) in cancers, including lung cancer. The ω-3 LCPUFAs, primarily consisting of eicosapentaenoic acid and docosahexaenoic acid, were found to modify inflammatory tumor microenvironment, induce cancer cell apoptosis and autophagy, and suppress tumor development when administered alone or with other therapeutical strategies. Although the precise anti-tumor mechanism has not been elucidated yet, ω-3 LCPUFAs are often used in the nutritional treatment of patients with cancer due to their ability to significantly improve patient's nutritional status, increase the sensitivity of tumor cells to treatments, and alleviate cancer-related complications. Here we present the key roles of ω-3 LCPUFAs as dietary supplementations in lung cancer, comprehensively review the recent progress on the underlying mechanisms of cancer cell regulation by ω-3 LCPUFAs, and introduce the application of ω-3 LCPUFAs in the clinical management of lung cancer and its malignant complications.

Article	Year
Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration. Journal of inflammation research\| PubMed ID: 35173457	2022
Metabolomic Profiling of Long-Chain Polyunsaturated Fatty Acid Oxidation in Adults with Retinal Vein Occlusion: A Case-Control Study. The American journal of clinical nutrition\| PubMed ID: 37454758	2023
Regulation of the Function and Expression of EpCAM. Biomedicines\| PubMed ID: 38791091	2024
UBR1 promotes anaplastic thyroid carcinoma progression via stabilizing YAP through monoubiquitylation. Scientific reports\| PubMed ID: 39174635	2024
Roles and therapeutic opportunities of ω-3 long-chain polyunsaturated fatty acids in lung cancer. iScience\| PubMed ID: 39834867	2025

Ziyu Jiang

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