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Nasopharyngeal carcinoma (NPC) is one of the most common tumors of head and neck in the Southeast Asia. PD-L1-dependent immune escape plays a critical role involved in NPC development. BPIFB1 has previously reported to take tumor-suppressive actions on NPC cell proliferation and migration. Nonetheless, the function of BPIFB1 in immune escape remains largely elusive. Expression pattern on mRNA and protein levels of target genes in NPC patients’ samples and cell lines were examined by qRT-PCR, western blot, and immunohistochemistry staining, respectively. The assessment of CD8+ T-cell apoptosis and expression was determined by flow cytometry. Molecular interactions were verified using chromatin immunoprecipitation (ChIP) and luciferase reporter assay. BPIFB1 was downregulated in NPC tumor tissues, exhibiting a negative correlation of PD-L1. Overexpression of BPIFB1 significantly inhibited the expression of PD-L1, suppressing the apoptosis and enhancing the expression of CD8+ T cells. Mechanistically, BPIFB1 was found to repress the expression of STAT1, which was identified to be an upstream activator of PD-L1. Furthermore, the EBV-encoded miR-BART4 overexpressed in NPC cells could directly target and inhibit BPIFB1. This study provided a comprehensive understanding of the molecular mechanism for the upstream and downstream pathway of BPIFB1 related with immune escape, indicating a novel approach for the treatment of NPC. [ABSTRACT FROM AUTHOR]

• The abnormal expression of piRNA and PIWI protein in diabetes and cardiovascular disease is associated with disease progression. • Serum extracellular vesicles-related piRNA has been detected in a surprisingly stable form and defined as a potential disease biomarker and a novel therapeutic target in CVD. • piRNA promotes the occurrence and development of CVD mainly through piRNA/LINE-1/AKT, AKT and AMPK signal pathways. Cardiovascular disease (CVD) is still one of the most significant diseases and is a considerable threat to human health globally. PIWI-interacting RNAs (piRNAs) are novel small noncoding RNAs (ncRNAs) traditionally considered to be specifically expressed in the germline of many animal species and involved in the maintenance of germline stem cells and spermatogenesis. Although little is known about the origin and action of piRNAs and PIWI proteins in somatic cells, these molecules are emerging as readily available biomarkers for the diagnosis and treatment of cardiac injury and multiform CVD. Accumulating evidence reveals that piRNAs and PIWI proteins are associated with some molecular and cellular pathways in CVD. Here, we summarize recent evidence and evaluate the molecular mechanism of the involvement of piRNAs and PIWI proteins in CVD. [ABSTRACT FROM AUTHOR]

Heat‐shock protein B1 (HSPB1) is a multifunctional protein that protects against oxidative stress; however, its function in antioxidant pathways remains largely unknown. Here, we sought to determine the roles of HSPB1 in H9c2 cells subjected to oxidative stress. Using nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis, we found that increased HSPB1 expression promoted the reduced states of glutathione reductase (GR), peroxiredoxin 1 (Prx1), and thioredoxin 1, whereas knockdown of HSPB1 attenuated these responses following oxidative stress. Increased HSPB1 expression promoted the activation of GR and thioredoxin reductase. Conversely, knockdown of HSPB1 attenuated these responses following oxidative stress. Importantly, overexpression of HSPB1 promoted the complex formation between HSPB1 and oxidized Prx1, leading to dephosphorylation of STE‐mammalian STE20‐like kinase 1 (MST1) in H9c2 cells exposed to H2O 2, whereas downregulation of HSPB1 induced the opposite results. Mechanistically, HSPB1 regulated the Hippo pathway by enhancing the dephosphorylation of MST1, resulting in reduced phosphorylation of LATS1 and Yes‐associated protein (YAP). Moreover, HSPB1 regulated YAP‐dependent gene expression. Thus, HSPB1 promoted the reduced state of endogenous antioxidant pathways following oxidative stress in H9c2 cells and improved the redox state of the cytoplasm via modulation of the Hippo signaling pathway. (1)Our study found for the first time that heat‐shock protein B1 (HSPB1) upholds the reduced state of the GSH‐glutaredoxin system and thioredoxin system in oxidative stress injury in H9c2 cells; (2)that HSPB1 interacts with oxidized peroxiredoxin 1 (Prx1); (3)and that HSPB1 inhibited phosphorylation of the Hippo signaling pathway by improving the cytoplasm reduced state and increasing the level of reduced Prx1. [ABSTRACT FROM AUTHOR]