Hypoxia conduces the glioma progression by inducing M2 macrophage polarization via elevating TNFSF9 level in a histone-lactylation-dependent manner.

Hypoxia is a critical factor contributing to a poor prognosis and challenging glioma therapy. Previous studies have indicated that hypoxia drives M2 polarization of macrophages and promotes cancer progression in various solid tumors. However, the more complex and diverse mechanisms underlying this process remain to be elucidated. Here, we aimed to examine the functions of hypoxia in gliomas and preliminarily investigate the underlying mechanisms of M2 macrophage polarization caused by hypoxia. We found that hypoxia significantly enhances the malignant phenotypes of U87 and U251 cells by regulating glycolysis. In addition, hypoxia mediated accumulation of the glycolysis product [lactic acid (LA)], which is subsequently absorbed by macrophages to induce its M2 polarization, and this process is reverted by both the glycolysis inhibitor and silenced monocarboxylate transporter (MCT-1) in macrophages, indicating that M2 macrophage polarization is associated with the promotion of glycolysis by hypoxia. Interestingly, we also found that hypoxia mediated LA accumulation in glioma cells upon uptake by macrophages upregulates H3K18La expression and promotes tumor necrosis factor superfamily member 9 (TNFSF9) expression in a histone-lactylation-dependent manner based on the results of chromatin immunoprecipitation sequencing (ChIP seq) enrichment analysis. Subsequent in vitro and in vivo experiments further indicated that TNFSF9 facilitated glioma progression. Mechanistically, hypoxia-mediated LA accumulation in glioma cells is taken up by macrophages and then induces its M2 macrophage polarization by regulating TNFSF9 expression via MCT-1/H3K18La signaling, thus facilitating the malignant progression of gliomas.NEW & NOTEWORTHY Our study revealed that hypoxia induces the production of LA accumulation through glycolysis in glioma cells, which is subsequently absorbed by macrophages and leads to its M2 polarization via the MCT-1/H3K18La/TNFSF9 axis, ultimately significantly promoting the malignant progression of glioma cells. These findings are novel and noteworthy as they provide insights into the connection between energy metabolism and epigenetics in gliomas.

Knockdown of UCA1 attenuated the progression of alcoholic fatty disease by sponging miR-214.

Alcoholic fatty liver (AFL) is the initial manifestation of Alcoholic liver disease which can develop into alcoholic cirrhosis even extensive necrosis of liver cells, which induces liver failure finally. This study aims to focus on the role of long noncoding RNA UCA1 in AFL and further explored possible mechanism of this disease. We first downloaded GSE28619 to identify the expression of UCA1 in patients with AFL and use lncRNAs microarray to confirm UCA1 expression in serum of patients with AFL. Then we established ethanol-induced L02 cell model to mimic hepatocyte injury condition. By conducting qRT-PCR, we measured the expression of LncRNA UCA1 and miR-214 in serum of patients and ethanol-induced L02 cell. MTT assay, transwell migration, ELISA, qRT-PCR, and western blotting analysis were applied to evaluating the effect of UCA1 on ethanol-induced L02 cell. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. In this study, we first detected the expression of UCA1 was up-regulated in serum of patients with AFL and ethanol-induced L02 cells. And knockdown of UCA1 reversed the inhibiting effect of ethanol on the biological behavior of L02 cells including cell proliferation, migration, and apoptosis. Besides, lncRNA UCA1 regulated the expression of KLF5 by sponging miR-214. LncRNA UCA1 regulated the biological behavior of ethanol-induced L02 cells by sponging miR-214, which may provide novel therapeutic strategies for alcoholic fatty liver.

In Silico Analysis of the Correlation of KIF2C with Prognosis and Immune Infiltration in Glioma.

Glioblastoma (GBM) is one of the most commonly pivotal malignant caners. Numerous reports have revealed the crucial roles of immune infiltration in the initiation and progression of GBM. In this study, we first identified differentially expressed genes (DEGs) in the progression of GBM using CGGA databases. Totally, 156 upregulated DEGs and 251 downregulated DEGs were revealed. By constructing a protein-protein interaction network, KIF2C was identified as a hub gene in GBM. Further analysis revealed an evidently positive association existing in KIF2C expression and the advanced stages of gliomas. Higher expression of KIF2C was in WHO grade IV samples relative to that in grade III and grade II samples. In addition, our results showed that KIF2C was higher in IDH1 wild-type samples than IDH1 mutant glioma samples, in 1p/19q noncodel samples than 1p/19q code glioma samples, and in recurrent samples than primary glioma samples. Moreover, our results showed that higher expression of KIF2C correlated with shorter survival time in both primary and recurrent gliomas and could act as a potential biomarker for the prognosis of GBM. Further analysis demonstrated that higher expression of KIF2C was related to higher levels of endothelial cell, T cell CD8+ naïve, common lymphoid progenitor, T cell CD4+ Th2, T cell CD4+ Th2, macrophage, macrophage M1, T cell CD4+ memory, and T cell CD4+ effector memory, but was related to lower levels of NK cell, B cell plasma, T cell CD4+ Th1, T cell regulatory (Tregs), neutrophil, and T cell NK. We thought this study could provide potential biomarkers for the prediction of prognosis and immune infiltration of gliomas.