Comprehensive Characterization of HATs and HDACs in Human Cancers Reveals Their Role in Immune Checkpoint Blockade.

Histone acetylation that controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs), as one of major epigenetic mechanisms controls transcription and its abnormal regulation was implicated in various aspects of cancer. However, the comprehensive understanding of HDACs and HATs in cancer is still lacking. Systematically analysis through 33 cancer types based on next-generation sequence data reveals heterogeneous expression pattern of HDACs and HATs across different cancer types. In particular, HDAC10 and HDAC6 show significant downregulation in most cancers. Principal components analysis (PCA) of pan-cancer reveals significant difference of HDACs and HATs between normal tissues and normal tissue adjacent to the tumor. The abnormal expression of HDACs and HATs was partially due to CNV and DNA methylation in multiple types of cancer. Prognostic significance (AUC reached 0.736) of HDACs and HATs demonstrates a five-gene signature including KAT2A, HAT1, KAT5, CREBBP and SIRT1 in KIRC. Analysis of NCI-60 drug database reveals the cytotoxic effect of several drugs are associated with dysregulated expression of HDACs and HATs. Analysis of immune infiltration and immunotherapy reveals that KAT2B and HDAC9 are associated with immune infiltration and immunotherapy. Our analysis provided comprehensive understanding of the regulation and implication of HDACs and HATs in pan-cancer. These findings provide novel evidence for biological investigating potential individual HDACs and HATs in the development and therapy of cancer in the future.

The 3' Non-Coding Sequence Negatively Regulates PD-L1 Expression, and Its Regulators Are Systematically Identified in Pan-Cancer.

The 3'-untranslated region (3'-UTR) of PD-L1 is significantly longer than the coding sequences (CDSs). However, its role and regulators have been little studied. We deleted whole 3'-UTR region by CRISPR-Cas9. Prognostic analysis was performed using online tools. Immune infiltration analysis was performed using the Timer and Xcell packages. Immunotherapy response prediction and Cox regression was performed using the R software. MicroRNA network analysis was conducted by the Cytoscape software. The level of PD-L1 was significantly and dramatically up-regulated in cells after deleting the 3'-UTR. Additionally, we discovered a panel of 43 RNA-binding proteins (RBPs) whose expression correlates with PD-L1 in the majority of cancer cell lines and tumor tissues. Among these RBPs, PARP14 is widely associated with immune checkpoints, the tumor microenvironment, and immune-infiltrating cells in various cancer types. We also identified 38 microRNAs whose individual expressions are associated with PD-L1 across different cancers. Notably, miR-3139, miR-4761, and miR-15a-5p showed significant associations with PD-L1 in most cancer types. Furthermore, we revealed 21 m6A regulators that strongly correlate with PD-L1. Importantly, by combining the identified RBP and m6A regulators, we established an immune signature consisting of RBMS1, QKI, ZC3HAV1, and RBM38. This signature can be used to predict the responsiveness of cancer patients to immune checkpoint blockade treatment. We demonstrated the critical role of the 3'-UTR in the regulation of PD-L1 and identified a significant number of potential PD-L1 regulators across various types of cancer. The biomarker signature generated from our findings shows promise in predicting patient prognosis. However, further biological investigation is necessary to explore the potential of these PD-L1 regulators.

Validity of total polar compound and its three components in monitoring the evolution of epoxy fatty acids in frying oil: Fast food restaurant conditions.

This study evaluated the validity of total polar compounds (TPC) and its three components in monitoring the evolution of epoxy fatty acids in frying oil under fast food restaurant conditions. The content of epoxy fatty acids can be predicted using the TPC rather than oxidized triglyceride monomer. When TPC content reached 24 g/100 g, 25 g/100 g, and 27 g/100 g, the epoxy fatty acid content in oil was found to be 1.47-3.63 mg/g, 1.58-4.06 mg/g, and 1.83-5.08 mg/g, respectively. More epoxy fatty acids were generated in high oleic sunflower oil than in canola and cottonseed oil during frying. At current discarding points of TPC 24-27 g/100 g, its epoxy fatty acid content was 3.63-5.08 mg/g, which was lower than the limit of 7 mg/g recommended by Max Rubner-Institut in Germany. Our results indicate that the risk of epoxy fatty acids can be monitored using the current TPC index.

Investigation of oxidized triglyceride monomer (oxTGM) produced in deteriorated soybean oil at frying temperatures: A kinetic study.

This work evaluated the feasibility of total polar compound (TPC) and its five components to monitor the deterioration of soybean oil at frying temperatures, and traditional indicators were used as a reference. The preliminary correlation analysis showed that polar compounds accumulated earlier than classical oxidation products like the peroxide value (PV). Equations for two types of characteristic kinetic time, the induction time (turning point of sigmoid curve) and intersection time (intersection point of two tangent lines representing the initiation and propagation reaction), were also derived. Their mathematical difference and relationship were then evaluated. Based on the kinetic analysis, the overall cumulative process of oxidation products of triglycerides (oxTGM) was found to be 2.35%-12.35% earlier than that of fatty acids (PV). Our results supported the index of oxTGM in TPC to be a better indicator to monitor the deterioration of heated edible oil.

Mechanism and Function of Circular RNA in Regulating Solid Tumor Radiosensitivity.

Radiotherapy is an important tool in the treatment of malignant tumors, and exploring how to make radiotherapy more effective is a new way to break through the current bottleneck in the development of radiation oncology. Circular RNAs (circRNAs) are a special class of endogenous non-coding RNAs. Numerous studies have shown that circRNAs have shown great potential in regulating the biological functions of tumors, including proliferation, migration, invasion, and treatment resistance, and that differences in their expression levels are closely related to the clinical prognosis of tumor patients. This review systematically compares the mechanisms of circRNAs in the process of tumor development and radiosensitivity and provides insight into the clinical translation of circRNAs in radiotherapy.