High Expression of E2F4 Is an Adverse Prognostic Factor and Related to Immune Infiltration in Oral Squamous Cell Carcinoma

Zheng, Yicai; Fei, He

doi:10.1155/2022/4731364

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…E2F4 represses the MAPK signaling pathway by binding with EZH2, thereby inhibiting the progression of acute myeloid leukemia [ 42 ]. High expression of E2F4 is an unfavorable prognostic factor in oral squamous cell carcinoma [ 43 ]. E2F4 accelerates the progression of colorectal cancer by promoting AGAP2-AS1 expression [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics

Sun,

Zhang,

Shi

et al. 2023

Hereditas

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Background Glioma stem cells (GSCs) are responsible for glioma recurrence and drug resistance, yet the mechanisms underlying their maintenance remains unclear. This study aimed to identify enhancer-controlled genes involved in GSCs maintenance and elucidate the mechanisms underlying their regulation. Methods We analyzed RNA-seq data and H3K27ac ChIP-seq data from GSE119776 to identify differentially expressed genes and enhancers, respectively. Gene Ontology analysis was performed for functional enrichment. Transcription factors were predicted using the Toolkit for Cistrome Data Browser. Prognostic analysis and gene expression correlation was conducted using the Chinese Glioma Genome Atlas (CGGA) data. Two GSC cell lines, GSC-A172 and GSC-U138MG, were isolated from A172 and U138MG cell lines. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to detect H3K27ac of enhancers, and binding of E2F4 to target gene enhancers. Western blot was used to analyze protein levels of p-ATR and γH2AX. Sphere formation, limiting dilution and cell growth assays were used to analyze GSCs growth and self-renewal. Results We found that upregulated genes in GSCs were associated with ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) pathway activation, and that seven enhancer-controlled genes related to ATR pathway activation (LIN9, MCM8, CEP72, POLA1, DBF4, NDE1, and CDKN2C) were identified. Expression of these genes corresponded to poor prognosis in glioma patients. E2F4 was identified as a transcription factor that regulates enhancer-controlled genes related to the ATR pathway activation, with MCM8 having the highest hazard ratio among genes positively correlated with E2F4 expression. E2F4 bound to MCM8 enhancers to promote its transcription. Overexpression of MCM8 partially restored the inhibition of GSCs self-renewal, cell growth, and the ATR pathway activation caused by E2F4 knockdown. Conclusion Our study demonstrated that E2F4-mediated enhancer activation of MCM8 promotes the ATR pathway activation and GSCs characteristics. These findings offer promising targets for the development of new therapies for gliomas.

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Section: Discussionmentioning

confidence: 99%

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics

Sun,

Zhang,

Shi

et al. 2023

Hereditas

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Transforaminal posterior lumbar interbody fusion microscopic safe operating area: a three-dimensional model study based on computed tomography imaging

Wang,

Cui,

Sun

et al. 2024

J Orthop Surg Res

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Background Endoscopic spine lumbar interbody fusion (Endo-LIF) is well-regarded within the academic community. However, it presents challenges such as intraoperative disorientation, high rates of nerve damage, a steep learning curve, and prolonged surgical times, often occurring during the creation of the operative channel. Furthermore, the undefined safe operational zones under endoscopy continue to pose risks to surgical safety. We aimed to analyse the anatomical data of Kambin’s triangle via CT imaging to define the parameters of the safe operating area for transforaminal posterior lumbar interbody fusion (TPLIF), providing crucial insights for clinical practice. Methods We selected the L4–L5 intervertebral space. Using three-dimensional (3D), we identified Kambin’s triangle and the endocircle within it, and recorded the position of point ‘J’ on the adjacent facet joint as the centre ‘O’ of the circle shifts by angle ‘β.’ The diameter of the inscribed circle ‘d,’ the abduction angle ‘β,’ and the distances ‘L1’ and ‘L2’ were measured from the trephine’s edge to the exiting and traversing nerve roots, respectively. Results Using a trephine with a diameter of 8 mm in TPLIF has a significant safety distance. The safe operating area under the TPLIF microscope was also clarified. Conclusions Through CT imaging research, combined with 3D simulation, we identified the anatomical data of the L4–L5 segment Kambin’s triangle, to clarify the safe operation area under TPLIF. We propose a simple and easy positioning method and provide a novel surgical technique to establish working channels faster and reduce nerve damage rates. At the same time, according to this method, the Kambin’s triangle anatomical data of the patient’s lumbar spine diseased segments can be measured through CT 3D reconstruction of the lumbar spine, and individualised preoperative design can be conducted to select the appropriate specifications of visible trephine and supporting tools. This may effectively reduce the learning curve, shorten the time operation time, and improve surgical safety.

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High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma

Zhao

Chen

et al. 2024

CMM

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Background: To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD. Objective: In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation. Methods: We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. Result: In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18–2.1; P=0.002). And TLX1 [removed]HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells. Conclusion: An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.

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High Expression of E2F4 Is an Adverse Prognostic Factor and Related to Immune Infiltration in Oral Squamous Cell Carcinoma

Cited by 3 publications

References 35 publications

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics

Enhancer-driven transcription of MCM8 by E2F4 promotes ATR pathway activation and glioma stem cell characteristics

Transforaminal posterior lumbar interbody fusion microscopic safe operating area: a three-dimensional model study based on computed tomography imaging

High TLX1 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Lung Adenocarcinoma

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