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Glioma is a severe disease of the central nervous system. Although previous studies have identified the important role of the immune response in association with tumor intervention, it is still unknown whether PU.1, a transcription factor known for its role in myeloid differentiation and immune responses, is involved in the progression of glioma. In the present study, we found a significant increase in SPI1, the gene that encodes PU.1, in samples from patients with glioma. Through genotype‑phenotype association analysis several candidate factors that may mediate the role of PU.1 in glioma were identified. To further validate the association between PU.1 and glioma we found that the expression of BTK, a potential target of PU.1, was also upregulated in patients with glioma. We also demonstrated that various biological pathways could be involved in PU.1‑associated glioma by analyzing these potential targets in the Reactome database. These results provide evidence that PU.1 could serve a role in the progress of glioma through its transcriptional targets in multiple signaling pathways. Therefore, in addition to its role in hematopoietic linage development and leukemia, PU.1 appears to be involved in the regulation of glioma and potentially in other malignant cancers. [ABSTRACT FROM AUTHOR]

Objective: Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology. Methods: U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF). Results: OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1β and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results. Conclusions: KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among females. Dachshund Homolog 1 (DACH1) gene is regarded as an important tumor suppressor gene in breast cancer which plays an important regulatory role in the development disease progression, particularly in carcinomas. Circular RNAs (circRNAs) and microRNA (miRNA), regarded as a novel group of noncoding RNAs, are always involved in regulating gene expression. In this work, hsa_circ_0047604 expressed lower in breast cancer tissue and played the role of sponge of miR-548o. By this way, hsa_circ_0047604 could upregulate DACH1 to inhibit breast cancer. In conclusion, this study revealed that hsa_circ_0047604 acted as a tumor suppressor and regulated breast cancer progression via hsa_circ_0047604–miR-548o–DACH1 axis, which might provide a therapeutic method for breast cancer. [ABSTRACT FROM AUTHOR]

Background and Objective: Neurotrophin receptor‐interacting MAGE homologue (NRAGE) plays a crucial role in the regulation of bone metabolism. The present study investigated the regulation role of NRAGE on autophagy activation and periodontitis process during experimental periodontitis. Materials and Methods: Six‐week‐old wild‐type (WT) and NRAGE−/− mice were randomly divided into three time points in the periodontitis groups (0, 2, and 4 weeks). Histopathological changes were determined using the tooth mobility, hematoxylin and eosin (H&E) staining, and micro‐computed tomography (micro‐CT). Osteoclasts activation and number were investigated using tartrate‐resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real‐time quantitative PCR (RT‐PCR). The level of autophagy‐related gene expression was measured using immunohistochemistry, immunofluorescence, and RT‐PCR. Results: H&E staining and Micro‐CT showed that the destruction of the alveolar bone was considerably more severe in the NRAGE−/− group than the WT group after ligation. Tooth mobility in the NRAGE−/− group was obviously higher than that in the WT group. The activation and number of osteoclasts and the level of autophagy‐related gene expression in NRAGE−/− group were significantly higher than that in WT group. Conclusions: The present study showed that knockout of NRAGE induced autophagy‐related gene expression and accelerated the process of periodontitis disease via increasing the activity and differentiation of osteoclast. [ABSTRACT FROM AUTHOR]