Silencing UHRF1 Inhibits Cell Proliferation and Promotes Cell Apoptosis in Retinoblastoma Via the PI3K/Akt Signalling Pathway

Liu, Yang; Liang, Guodong; Zhou, Tingting; Liu, Zengshan

doi:10.1007/s12253-019-00656-7

Cited by 15 publications

(12 citation statements)

References 32 publications

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“…Therefore, we aimed to elucidate the roles and mechanisms of the regulation of UHRF1 in trophoblasts that further contribute to RPL. Previous studies have shown that UHRF1 can inhibit or promote the proliferation of many cancer cells and immune cells 23,26,47,48 . However, our results showed that the proliferative capacity of the trophoblasts was not affected by UHRF1 deficiency, which was confirmed by the detection of targeted DNA synthesis.…”

Section: Discussionsupporting

confidence: 60%

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Liu

Wang

et al. 2022

The FASEB Journal

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Trophoblasts play critical roles in establishment and maintenance of a normal pregnancy. Their dysfunction in early pregnancy is closely related to pregnancy‐related diseases, including recurrent pregnancy loss (RPL). Epigenetic modifications dynamically change during pregnancy; however, the role of the epigenetic modifier UHRF1 in trophoblast regulation remains unknown. This is the first study to show that UHRF1 expression was localized in the cytoplasm of cytotrophoblasts, syncytiotrophoblasts, and villi columns, and decreased in the villi of patients with RPL. The invasion and cell viability in a UHRF1 knockdown trophoblast cell line were significantly decreased. In addition, the mRNA expression profiles of Swan71 cells were partially altered by UHRF1 knockdown. The altered immune‐related genes were screened out and the pro‐inflammatory TH1‐type chemokine/cytokines CXCL2 and IL‐1β were identified as the most promising targets of UHRF1 in the trophoblasts, which were significantly increased in the UHRF1 knockdown Swan71 cells, villi, and serum from patients with RPL. The macrophages treated with the supernatants of UHRF1 knockdown Swan71 cells were polarized to the M1 phenotype and secreted high levels of pro‐inflammatory cytokines, which might be driven by the activated MyD88/NF‐κB signaling pathway and mediated by the increased expression of CXCR2 and IL‐1R1 (CXCL2 and IL‐1β receptors, respectively). In addition, the supernatants of UHRF1 knockdown Swan71 cells showed stronger chemotaxis to macrophages than those from the controls. Our findings highlight the previously unknown roles of UHRF1 as one of the key regulators on the trophoblasts and their cross‐talk with local immune cells, and demonstrate a potential approach for RPL intervention.

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Section: Discussionsupporting

confidence: 60%

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Liu

Wang

et al. 2022

The FASEB Journal

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“…On the contrary, CADM1, as a representative of 18 downregulated DEGs, was found to negatively regulate the phenotype of RB cells. Several previous studies have shown that UHRF1 is related to the occurrence and development of RB ( 19 , 20 ). This study reveals the key role of UHRF1 in RB from the perspective of bioinformatics, further supporting UHRF1 as a potential diagnostic and therapeutic biomarker for RB.…”

Section: Discussionmentioning

confidence: 98%

Exploration of retinoblastoma pathogenesis with bioinformatics

Zhang¹,

Zhou²,

Wang³

et al. 2021

Transl Cancer Res TCR

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Background: Differentially expressed genes (DEGs) from retinoblastoma (RB) tissues play key roles in the progression of RB. However, the role of DEGs in different subtypes and stages of RB has not yet been systematically analyzed.Methods: In this study, the DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were analyzed with regard to the different subtypes and stages of the disease.Results: Through comparison with adjacent tissues, a total of 78 upregulated genes and 155 downregulated genes from the RB tissues were identified across the 3 data sets. Gene set enrichment analysis (GSEA) showed that the 3 representative genes CDK1, CDC20, and BUB1, which were all upregulated, could promote the cell cycle in RB. Compared with adjacent tissues in GSE97508, a total of 19 gigantol-targeted genes were predicted to be upregulated in invasive RB tissues. On the other hand, DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were integrated with regard to invasiveness and stages of the disease, and another 19 DEGs were subsequently identified. Among these genes, UHRF1 was the only identified upregulated gene, while the other 18 were all downregulated genes. Cell Counting Kit-8 (CCK-8) experiment and GSEA results showed that UHRF1 can promote the proliferation and invasion of RB.Conversely, the downregulated representative gene CADM1 is a tumor suppressor gene, which can inhibit the progression of RB.Conclusions: This study indicated that the verified DEGs are continuously and consistently expressed in different subtypes and stages of RB. These DEGs may be the key to understanding the development and invasion of RB.

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“…By promoting proliferation and differentiation, UHRF1 regulates the VSMC phenotype, and it may hold therapeutic potential in vascular pathologies [66]. Silencing UHRF1 inhibits cell proliferation and promotes cell apoptosis in retinoblastoma through the PI3K/Akt signaling pathway [67]. UHRF1 is highly expressed in proliferating and cancer cells, and it has been identified as a novel AMPK gate-keeper in cellular metabolism by interacting with AMPK and suppressing its activity.…”

Section: Discussionmentioning

confidence: 99%

RNA Sequencing Analysis of Gene Expression by Electroacupuncture in Guinea Pig Gallstone Models

Hao

Dou

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Clinical studies have shown that electroacupuncture (EA) promotes gallbladder motility and alleviates gallstone. However, the mechanism underlying the effects of EA on gallstone is poorly understood. In this study, the mRNA transcriptome analysis was used to study the possible therapeutic targets of EA. Methods. Hartley SPF guinea pigs were employed for the gallstone models. Illumina NovaSeq 6000 platform was used for the RNA sequencing of guinea pig gallbladders in the normal group (Normal), gallstone model group (Model), and EA-treated group (EA). Differently expressed genes (DEGs) were examined separately in Model vs. Normal and EA vs. Model. DEGs reversed by EA were selected by comparing the DEGs of Model vs. Normal and EA vs. Model. Biological functions were enriched by gene ontology (GO) analysis. The protein-protein interaction (PPI) network was analyzed. Results. After 2 weeks of EA, 257 DEGs in Model vs. Normal and 1704 DEGs in EA vs. Model were identified. 94 DEGs reversed by EA were identified among these DEGs, including 28 reversed upregulated DEGs and 66 reversed downregulated DEGs. By PPI network analysis, 10 hub genes were found by Cytohubba plugin of Cytoscape. Quantitative real-time PCR (qRT-PCR) verified the changes. Conclusion. We identified a few GOs and genes that might play key roles in the treatment of gallstone. This study may help understand the therapeutic mechanism of EA for gallstone.

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Silencing UHRF1 Inhibits Cell Proliferation and Promotes Cell Apoptosis in Retinoblastoma Via the PI3K/Akt Signalling Pathway

Cited by 15 publications

References 32 publications

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy

Exploration of retinoblastoma pathogenesis with bioinformatics

RNA Sequencing Analysis of Gene Expression by Electroacupuncture in Guinea Pig Gallstone Models

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