This study aimed to elucidate the effect of bone marrow mesenchymal stem cell (BMSC) transplantation combined with the administration of Lugua polypeptide injection into the knee joint cavity to tr...

Effect of bone marrow mesenchymal stem cell transplantation combined with lugua polypeptide injection on osteoarthritis in rabbit knee joint.

BACKGROUND
Glioblastoma stem cells (GSCs) and their interplay with tumor-associated macrophages (TAMs) are responsible for malignant growth and tumor recurrence of Glioblastoma (GBM), but the underlying mechanisms are largely unknown.


METHODS
Cell viability, stemness, migration and invasion was measured in GSCs after knockdown of upstream stimulating factor 1 (USF1). Luciferase assay and chromatin immunoprecipitation qPCR were performed to determine the regulation of CD90 by USF1. Immunohistochemistry and immunofluorescent staining were used to examine the expression of USF1 and GSC markers, as well as the crosstalk between GSCs and TAMs. In addition, the interaction between GSCs and TAMs was confirmed using in vivo GBM models.


RESULTS
We show that USF1 promotes malignant glioblastoma phenotypes and GSCs-TAMs physical interaction by inducing CD90 expression. USF1 predicts a poor prognosis for glioma patients, and is upregulated in patient-derived GSCs and glioblastoma cell lines. USF1 overexpression increases the proliferation, invasion and neurosphere formation of GSCs and glioblastoma cell lines, while USF1 knockdown exerts an opposite effect. Further mechanistic studies reveal that USF1 promotes GSC's stemness by directly regulating CD90 expression. Importantly, CD90 of GSCs functions as an anchor for physical interaction with macrophage. Additionally, the USF1/CD90 signaling axis supports the GSCs and TAMs adhesion and immunosuppressive feature of TAMs, which in turn enhance the stemness of GSCs. Moreover, the overexpression of CD90 restores the stemness property in USF1 knockdown GSCs and its immunosuppressive microenvironment.


CONCLUSIONS
Our findings indicate that the USF1/CD90 axis might be a potential therapeutic target for the treatment of glioblastoma.

USF1/CD90 signaling in maintaining glioblastoma stem cells and tumor-associated macrophages adhesion.

Background Upstream transcription factor 1 (USF1) single-nucleotide polymorphisms (SNPs) are significantly associated with serum lipid levels in several different ethnic groups or populations, but their association with lipid levels and the risk of early-onset coronary artery disease (EOCAD) has not been reported in Han populations of southern China. Methods Six USF1 SNPs (rs3737787, rs2774276, rs2516839, rs2516838, rs1556259, and rs2516837) were genotyped by next-generation sequencing (NGS) techniques in 686 control subjects and 728 patients with EOCAD. Results The genotypic and allelic frequencies of the USF1 rs3737787 SNP were significantly different between the control and EOCAD groups. The subgroup analysis identified that the rs3737787T allele was related to a decreased risk of EOCAD, whereas the rs3737787C–rs2774276G–rs2516839A and rs3737787C–rs2774276G–rs2516839G haplotypes were related to an increased risk of EOCAD in men, and the rs3737787C–rs2774276G–rs2516839A and rs3737787T–rs2774276C–rs2516839A haplotypes were correlated with an increased risk of EOCAD in women (p < 0.05–0.01). Male rs3737787T allele carriers had lower low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) concentrations than the rs3737787T allele non-carriers (p < 0.01). The interactions of rs3737787 with alcohol consumption and rs2516839 with smoking affected serum TC and LDL-C levels in men, whereas the interaction of rs3737787 with alcohol consumption affected serum high-density lipoprotein cholesterol (HDL-C) levels and the rs2516839-smoking interaction affected serum TC levels in women (pI < 0.001). The expression levels of the USF1 mRNA, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) were significantly lower in controls than in patients with EOCAD, and rs3737787T allele carriers displayed lower IL-1β, TNF-α, IL-6, and USF1 mRNA expression levels than the rs3737787T allele non-carriers. In addition, IL-1β, TNF-α, and IL-6 expression levels were significantly positively correlated with USF1 mRNA levels (p < 0.01). Conclusion Sex-specific correlations were identified between the USF1 rs3737787T allele with blood lipid levels and the risk of EOCAD. The USF1 rs3737787T allele affects the risk of EOCAD by modulating serum lipid levels and the expression of inflammatory factors, including IL-1β, TNF-α, and IL-6.

/pdf/effects-of-usf1-snps-and-snp-environment-interactions-on-2sl0xiy1.pdf

Effects of USF1 SNPs and SNP–Environment Interactions on Serum Lipid Profiles and the Risk of Early-Onset Coronary Artery Disease in the Chinese Population

Liver cancer, including hepatocellular carcinoma (HCC), is a malignant tumor that has high rates of metastasis and mortality worldwide. Upstream transcription factor 1 (USF1) is a canonical transcription factor (TF) and is associated with the pathogenesis of several cancers, but its biological functions and molecular targets in HCC remain unclear. Huh7 cells that overexpress USF1 were used with whole transcriptome profiling through RNA sequencing and chromatin immunoprecipitation (ChIP) sequencing methods to investigate the downstream targets of USF1. Reverse transcription-quantitative PCR was then used to validate the downstream targets. The results showed that USF1 significantly regulates 350 differentially expressed genes (DEGs). The upregulated DEGs were primarily protein-coding genes enriched in immune and inflammation response pathways, while the downregulated DEGs were mainly coding long non-coding (lnc)RNAs, indicating the regulatory function of USF1. It was also demonstrated that USF1 directly binds to the promoter region of 2,492 genes, which may be involved in the viral progression and cell proliferation pathways. By integrating these two datasets, 16 overlapped genes were detected, including downregulated lncRNA-NEAT1 and upregulated TF-ETV5. The downregulated lncRNA-NEAT1 showed reverse expression pattern and prognosis result compared with that of USF1 in patients with liver cancer, while upregulated TF-ETV5 showed consistent results with USF1. Promoter region motif analysis indicated that ETV5 has more binding motifs and genes than USF1 itself for USF1-regulated DEGs, indicating that USF1 may indirectly modulate gene expression by regulating ETV5 expression in Huh7 cells. The study also validated the direct interaction between USF1 and the promoter of ETV5 using ChIP-qPCR. In summary, the results demonstrated that USF1 binds to the promoter region of thousands of genes and affects a large part of DEGs indirectly. Downstream genes, including lncRNA-NEAT1 and TF-ETV5, may also have potential functions in the regulated network by USF1 and have potential functions in the progression of HCC. The present findings suggested that USF1 and its downstream targets could be potential targets for HCC therapy in the future.

USF1 modulates transcription and cellular functions by regulating multiple transcription factors in Huh7 cells

LncRNAs has been demonstrated to modulate neoplastic development by modulating downstream miRNAs and functional genes. In this study, we aimed to detect the interaction among lncRNA ZFAS1 miR-296-5p and USF1. We explored the proliferation, migration and invasion of cholangiocarcinoma. The differentially expressed ZFAS1 was discovered in both tissues and cell lines by qRT-PCR. The targeting relationship between miR-296-5p and ZFAS1 or USF1 was validated by dual-luciferase assay. The impact of ZFAS1 on CCA cell proliferation was observed by CCK-8 assay. The protein expression of USF1 was determined by Western blot. The effects of ZFAS1, miR-296-5p and USF1 on tumour growth were further confirmed using xenograft model. LncRNA ZFAS1 expression was relatively up-regulated in tumour tissues and cells while miR-296-5p was significantly down-regulated. Knockdown of ZFAS1 significantly suppressed tumour proliferation, migration, invasion and USF1 expression. Overexpressed miR-296-5p suppressed cell proliferation and metastasis. Knockdown of USF1 inhibited cell proliferation and metastasis and xenograft tumour growth. In conclusion, ZFAS1 might promote cholangiocarcinoma proliferation and metastasis by modulating USF1 via miR-296-5p.

Up-regulation of ZFAS1 indicates dismal prognosis for cholangiocarcinoma and promotes proliferation and metastasis by modulating USF1 via miR-296-5p.

The current study mainly aims to evaluate the expression pattern and underlying mechanism of upstream stimulating factor 1 (USF1) in the muscle tissues of knee osteoarthritis (KOA) patients. In accordance with previous findings, our data showed that muscle strength was significantly decreased in KOA patients compared with controls. Furthermore, several inflammatory factors, including tumor necrosis factor α (TNFα), IL-8, IL-6 and MCP-1, were associated with reduced muscle strength in KOA patients. Not surprisingly, NF-κB signaling was significantly activated in the muscle tissues of KOA patients compared with control individuals. Furthermore, we showed that USF1 was increased in the muscles of KOA patients compared with controls. More importantly, overexpression of USF1 in primary human skeletal muscle cells significantly increased the activation of NF-κB signaling as well as the levels of pro-inflammatory factors. In summary, we showed novel data that the upregulation of USF1 promoted NF-κB activation-induced inflammatory responses in muscle tissues of KOA patients.

/pdf/usf1-promotes-the-development-of-knee-osteoarthritis-by-57n22ol5qj.pdf

USF1 promotes the development of knee osteoarthritis by activating the NF-κB signaling pathway.

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USF1 promotes the development of knee osteoarthritis by activating the NF-κB signaling pathway.