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

: Immunotherapy targeting PD-1/PD-L1 represents a breakthrough in the treatment of lung cancer. Pyruvate kinase M2 (PKM2) is not only a critical player in glycolysis, but also conducive to tumor progression and immune response. While both have been linked to lung adenocarcinoma (AC), the correlation and clinical significance of PKM2 and PD-L1 expression in human lung AC tissues remains not entirely explored. : Expression of PKM2 and PD-L1 proteins were detected by immunohistochemistry in 74 lung AC cases and the corresponding noncancerous tissues. Simultaneously, multiplex immunofluorescence was used to detect PKM2, PD-L1, CK, CD3, and CD68 in the lung AC tissues. We measured expression patterns and co-localization of these markers, evaluating their association with clinicopathological features and overall survival. Validation of findings was conducted using mRNA expression data from The Cancer Genome Atlas (TCGA) of 515 lung AC cases. : High expression of PKM2 in tumor cells was significantly related with lymph node metastasis and TNM stage (p=0.035, p=0.017, respectively). Moreover, PKM2 expression in tumor cells was positively correlated with tumor PD-L1 expression. High expression of PKM2, PD-L1 in tumor cells and immune cells predicted high mortality rate and poorer survival rates, respectively. Additionally, multivariate Cox regression models indicated that high expression of PKM2 in tumor cells was an independent prognostic factor. Based on TCGA genomic data, high PKM2 mRNA expression was significantly associated with poorer survival (p=0.001). : High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict poorer survival rates in patients with lung AC.

High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma.

Radiotherapy has been widely used to treat various cancers, but its efficacy depends on the individual involved. Traditional gene-based machine-learning models have been widely used to predict radiosensitivity. However, there is still a lack of emerging powerful models, artificial neural networks (ANN), in the practice of gene-based radiosensitivity prediction. In addition, ANN may overfit and learn biologically irrelevant features.

Prediction of radiosensitivity and radiocurability using a novel supervised artificial neural network.

The development of intensive care medicine is inseparable from the diversified monitoring data. Intensive care medicine has been closely integrated with data since its birth. Critical care research requires an integrative approach that embraces the complexity of critical illness and the computational technology and algorithms that can make it possible. Considering the need of standardization of application of big data in intensive care, Intensive Care Medicine Branch of China Health Information and Health Care Big Data Society, Standard Committee has convened expert group, secretary group and the external audit expert group to formulate Chinese Experts' Consensus on the Application of Intensive Care Big Data (2022). This consensus makes 29 recommendations on the following five parts: Concept of intensive care big data, Important scientific issues, Standards and principles of database, Methodology in solving big data problems, Clinical application and safety consideration of intensive care big data. The consensus group believes this consensus is the starting step of application big data in the field of intensive care. More explorations and big data based retrospective research should be carried out in order to enhance safety and reliability of big data based models of critical care field.

Chinese experts' consensus on the application of intensive care big data.

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
High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma. Journal of Cancer\| PubMed ID: 32489463	2020
Prediction of radiosensitivity and radiocurability using a novel supervised artificial neural network. BMC cancer\| PubMed ID: 36451111	2022
Chinese experts' consensus on the application of intensive care big data. Frontiers in medicine\| PubMed ID: 38264049	2023
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

Yu Yuan

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