Knightholcomb5630

In this review, we address the possible involvement of IRF2BP2 in tumorigenesis through its regulation of important pathways involved in tumor development.Polycomb group (PcG) of proteins are a group of highly conserved epigenetic regulators involved in many biological functions, such as embryonic development, cell proliferation, and adult stem cell determination. icFSP1 cell line PHD finger protein 19 (PHF19) is an associated factor of Polycomb repressor complex 2 (PRC2), often upregulated in human cancers. In particular, myeloid leukemia cell lines show increased levels of PHF19, yet little is known about its function. Here, we have characterized the role of PHF19 in myeloid leukemia cells. We demonstrated that PHF19 depletion decreases cell proliferation and promotes chronic myeloid leukemia (CML) differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through a direct regulation of the cell cycle inhibitor p21. Furthermore, we observed that MTF2, a PHF19 homolog, partially compensates for PHF19 depletion in a subset of target genes, instructing specific erythroid differentiation. Taken together, our results show that PHF19 is a key transcriptional regulator for cell fate determination and could be a potential therapeutic target for myeloid leukemia treatment.Mutation of the telomerase reverse transcriptase (TERT) promoter has been demonstrated as an unfavorable prognostic marker in patients with isocitrate dehydrogenase wild-type (IDHwt) glioma. This study aimed to investigate the immune role of TERT promoter mutation status which could improve prognostic prediction in IDHwt. TERT mutation status, IDH mutation, and 1p-19q codeletion status data were obtained from 614 glioma cases from the Cancer Genome Atlas, and 325 cases from the Chinese Glioma Genome Atlas. The same information was obtained from 49 clinical glioma tissues. TERT mutation is preferentially present in glioblastoma and IDH-wt gliomas and is associated with poor prognosis. Moreover, TERT mutation was associated with infiltration of neutrophils and expression of neutrophil chemokines. which might partially contribute to the poor outcome in IDH-wt glioma. Furthermore, patients with IDH-wt glioma did not harbor increased peripheral neutrophils, implying that the infiltrated neutrophil in the tumor environment might due to cytokine chemotaxis. In this study, we hereby propose that TERT mutation might be a molecular driver of the dysfunctional immune microenvironment in IDH-wt glioma. TERT mutation may be a potential immune therapeutic target for optimizing treatment combinations and patient selection for glioma immunotherapy.Abnormal accumulation of misfolded tau aggregates is a pathological hallmark of various tauopathies including Alzheimer's disease (AD). Although tau is a cytosolic microtubule-associated protein enriched in neurons, it is also found in extracellular milieu, such as interstitial fluid, cerebrospinal fluid, and blood. Accumulating evidence showed that pathological tau spreads along anatomically connected areas in the brain through intercellular transmission and templated misfolding, thereby inducing neurodegeneration and cognitive dysfunction. In line with this, the spatiotemporal spreading of tau pathology is closely correlated with cognitive decline in AD patients. Although the secretion and uptake of tau involve multiple different pathways depending on tau species and cell types, a growing body of evidence suggested that tau is largely secreted in a vesicle-free forms. In this regard, the interaction of vesicle-free tau with membrane is gaining growing attention due to its importance for both of tau secretion and uptake as well as aggregation. Here, we review the recent literature on the mechanisms of the tau-membrane interaction and highlights the roles of lipids and proteins at the membrane in the tau-membrane interaction as well as tau aggregation.Inflammation is a crucial mediator of atherosclerosis, and several therapeutic methods that focus on inflammatory cytokines, including interleukin-1β (IL-1β), have proven effective in preventing atherogenesis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs (ncRNAs) that can exert critical functions in the regulation of atherosclerosis. Here, using circRNA sequencing, we revealed that circRNA circDENND1B (mmu_circ_0000081) is a promising novel mediator of atherosclerosis in mouse. The expression of circDENND1B is negatively related to the progression of atherosclerosis and foam cell formation, and the upregulation of circDENND1B significantly alleviates foam cell formation induced by ox-LDL by promoting cholesterol efflux. Moreover, circDENND1B participates in the anti-atherosclerotic effect of IL-1β monoclonal antibody (IL-1β mAb), both in vivo and in vitro. With bioinformatic prediction and RNA pull-down assays, we determined that circDENND1B sponges mmu-miR-17-5p to promote Abca1 expression in cells treated with IL-1β mAb. Our study revealed that circDENND1B, a novel regulator of cholesterol efflux, is a potential therapeutic target in atherosclerosis and provides new insights into the interaction between inflammation and cholesterol transport.Recurrence and metastasis seriously affects the prognosis of patients with tumors, and the epithelial-to-mesenchymal transition (EMT) plays a key role in promoting tumor invasion and metastasis. Previous studies have showed that β-arrestin1 acted as a tumor-promoting factor in multiple types of tumor. However, the exact role and mechanism of β-arrestin1 in colorectal cancer (CRC) progression remains to be elucidated. Our research aimed to explore the potential mechanism underlying the role of β-arrestin1 in CRC metastasis. The expression of β-arrestin1 was investigated in both primary and metastatic CRC tissues using the GSE41258 database, and it was revealed that CRC patients with liver/lung metastasis had a higher expression level of β-arrestin1, and the expression level of β-arrestin1 was inversely correlated with the prognosis of CRC patients. Further in vitro mechanism studies indicated that β-arrestin1 had the ability to promote the migration of CRC cells through regulating the EMT process by activating Wingless/integration-1 (Wnt)/β-catenin signaling pathways.