JAG1, Regulated by microRNA-424-3p, Involved in Tumorigenesis and Epithelial–Mesenchymal Transition of High Proliferative Potential-Pituitary Adenomas

Chen, Yiyuan; Li, Bin; Feng, Jiaxuan; Fang, Qiuyue; Cheng, Jianhua; Xie, Weiyan; Li, Chuzhong; Cheng, Sen; Zhang, Yazhou; Gao, Hua

doi:10.3389/fonc.2020.567021

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…However, while molecular-targeted drugs such as anlotinib and sorafenib induce sensitization to RFA or radiotherapy by inhibiting the EMT of malignant tumor cells, these molecules do not inhibit EMT as iDNMT does ( Roskoski, 2020 ; Roskoski, 2021 ; Roskoski, 2022 ). The most specific molecular mechanism of the targeted drugs in this study, and one of our most important findings, is the induction of EMT in malignant cells ( Chen et al, 2020 ). Therefore, we conclude that iDNMT is an important pharmacological tool for downregulating PSEN-1 expression via miR-27-3p, thereby inhibiting the cleavage and activation of the Notch protein, thus inhibiting the EMT of LSCC cells.…”

Section: Discussionmentioning

confidence: 69%

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

et al. 2022

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Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p′s promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p′s promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.

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Section: Discussionmentioning

confidence: 69%

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

et al. 2022

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“…The libraries were sequenced on an Illumina Hiseq X platform, and then 150 bp paired-end reads were generated. Clean reads were mapped to the human reference genome (NCBI37/hg19) using hisat2 (v2.0.5) to obtain read counts/FPKM/TPM for each noticed gene [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

Analysis of the Prognostic and Immunological Role of HSPB1 in Pituitary Adenoma: A Potential Target for Therapy

Zhao

Chen

et al. 2023

Medicina

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Background and Objectives: The diagnosis and treatment of pituitary adenomas with cavernous sinus invasion pose significant challenges for clinicians. The objective of this study is to investigate the expression profile and prognostic value of HSPB1 (heat shock protein beta-1) in pituitary adenomas with invasive and non-invasive features. Additionally, we aim to explore the potential relationship between HSPB1 expression and immunological functions in pituitary adenoma. Materials and Methods: A total of 159 pituitary adenoma specimens (73 invasive tumours and 86 non-invasive tumours) underwent whole-transcriptome sequencing. Differentially expressed genes and pathways in invasive and non-invasive tumours were analysed. HSPB1 was subjected to adequate bioinformatics analysis using various databases such as TIMER, Xiantao and TISIDB. We investigated the correlation between HSPB1 expression and immune infiltration in cancers and predicted the target drug of HSPB1 using the TISIDB database. Results: HSPB1 expression was upregulated in invasive pituitary adenomas and affected immune cell infiltration. HSPB1 was significantly highly expressed in most tumours compared to normal tissues. High expression of HSPB1 was significantly associated with poorer overall survival. HSPB1 was involved in the regulation of the immune system in most cancers. The drugs DB11638, DB06094 and DB12695 could act as inhibitors of HSPB1. Conclusions: HSPB1 may serve as an important marker for invasive pituitary adenomas and promote tumour progression by modulating the immune system. Inhibitors of HSPB1 expression are currently available, making it a potential target for therapy in invasive pituitary adenoma.

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“…qRT-PCR was performed on the Applied Bio-systems 7500 Fast System (Life Technologies, Carlsbad, CA, USA). The fold-change in differential expression for each gene was calculated using the comparative CT method (2 −∆∆CT method), R package: “pcr”, , accessed on 5 May 2020 reference gene: “ GAPDH ,” reference group: “Somatotroph Adenoma” [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas

Chen

Yao

et al. 2022

IJMS

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Somatotroph adenomas are the leading cause of acromegaly, with the nearly sparsely granulated somatotroph subtype belonging to high-risk adenomas, and they are less responsive to medical treatment. The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. In this study, we identified the characteristic profiling of the integrated stress response in translocation and translation initiation factor activity in somatotroph adenomas, normal pituitary, or other adenoma subtypes through proteomics. Immunohistochemistry exhibited the differential significance and the priority of eukaryotic translation initiation factor 2β (EIF2β) in somatotroph adenomas compared with gonadotroph and corticotroph adenomas. Differentially expressed genes based on the level of EIF2β in somatotroph adenomas were revealed. MetaSape pathways showed that EIF2β was involved in regulating growth and cell activation, immune system, and extracellular matrix organization processes. The correlation analysis showed Spearman correlation coefficients of r = 0.611 (p < 0.001) for EIF2β and eukaryotic translation initiation factor 2 alpha kinase 1 (HRI), r = 0.765 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 2 (PKR), r = 0.813 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 3 (PERK), r = 0.728 (p < 0.001) for GCN2, and r = 0.732 (p < 0.001) for signal transducer and activator of transcription 3 (STAT3). Furthermore, the invasive potential in patients with a high EIF2β was greater than that in patients with a low EIF2β (7/10 vs. 4/18, p = 0.038), with a lower immune-cell infiltration probability (p < 0.05). The ESTIMATE algorithm showed that the levels of activation of the EIF2 pathway were negatively correlated with the immune score in somatotroph adenomas (p < 0.001). In in vitro experiments, the knockdown of EIF2β changed the phenotype of somatotroph adenomas, including cell proliferation, migration, and the secretion ability of growth hormone/insulin-like growth factor-1. In this study, we demonstrate that the ISR is pivotal in somatotroph adenomas and provide a rationale for implementing ISR-based regimens in future treatment strategies.

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JAG1, Regulated by microRNA-424-3p, Involved in Tumorigenesis and Epithelial–Mesenchymal Transition of High Proliferative Potential-Pituitary Adenomas

Cited by 10 publications

References 31 publications

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

Analysis of the Prognostic and Immunological Role of HSPB1 in Pituitary Adenoma: A Potential Target for Therapy

The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas

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