Inhibition of eIF4E signaling by ribavirin selectively targets lung cancer and angiogenesis

Tan, Hongxia; He, Li; Cheng, Zhenshun

doi:10.1016/j.bbrc.2020.05.127

Cited by 18 publications

(11 citation statements)

References 34 publications

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“…Thereinto, most of these drugs are involved in angiogenesis inhibition, e.g., arbutin [ 42 ], entinostat [ 43 ], sulforaphane [ 44 ], and sunitinib [ 45 ], which have been demonstrated to suppress angiogenesis in tumor treatments effectively. Triclosan [ 46 ] and ribavirin [ 47 ] had been identified as effectual angiogenesis inhibitors. Cyclosporine promoted osteogenic differentiation of periodontal membrane stem cells and curbed angiogenesis [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Diagnostic Markers in Infantile Hemangiomas

Huang

Chen

Gao

et al. 2022

Journal of Oncology

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Background. Infantile Hemangiomas (IHs) are common benign vascular tumors of infancy that may have serious consequences. The research on diagnostic markers for IHs is scarce. Methods. The “limma” R package was applied to identify differentially expressed genes (DEGs) in developing IHs. Plugin ClueGO in Cytoscape software performed functional enrichment of DEGs. The Search Tool for Retrieving Interacting Genes (STRING) database was utilized to construct the PPI network. The least absolute shrinkage and selection operator (LASSO) regression model and support vector machine recursive feature elimination (SVM-RFE) analysis were used to identify diagnostic genes for IHs. The receiver operating characteristic (ROC) curve evaluated diagnostic genes’ discriminatory ability. Single-gene based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted by Gene Set Enrichment Analysis (GSEA). The chemicals related to the diagnostic genes were excavated by the Comparative Toxicogenomics Database (CTD). Finally, the online website Network Analyst was used to predict the transcription factors targeting the diagnostic genes. Results. A total of 205 DEGs were singled out from IHs samples of 6-, 12-, and 24-month-old infants. These genes principally participated in vasculogenesis and development-related, endothelial cell-related biological processes. Then we mined 127 interacting proteins and created a network with 127 nodes and 251 edges. Furthermore, LASSO and SVM-RRF algorithms identified five diagnostic genes, namely, TMEM2, GUCY1A2, ISL1, WARS, and STEAP4. ROC curve analysis results indicated that the diagnostic genes had a powerful ability to distinguish IHs samples from normal samples. Next, the results of GSEA for a single gene illustrated that all five diagnostic genes inhibited the “valine, leucine, and isoleucine degradation” pathway in the development of IHs. WARS, TMEM2, and STEAP4 activated the “blood vessel development” and “vasculature development” in IHs. Subsequently, inhibitors targeting TMEM2, GUCY1A2, ISL1, and STEAP4 were mined. Finally, 14 transcription factors regulating GUCY1A2, 14 transcription factors regulating STEAP4, and 26 transcription factors regulating ISL1 were predicted. Conclusion. This study identified five diagnostic markers for IHs and further explored the mechanisms and targeting drugs, providing a basis for diagnosing and treating IHs.

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Section: Discussionmentioning

confidence: 99%

Identification of Diagnostic Markers in Infantile Hemangiomas

Huang

Chen

Gao

et al. 2022

Journal of Oncology

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“…Overexpression of EIF4E results in a dramatic increase in VEGF and fibroblast growth factor-2 (FGF-2), two potent angiogenic agents [60,61]. In contrast, blocking EIF4E signaling selectively inhibited angiogenesis in human endothelial cells in vitro [62] and in vivo [63,64].…”

Section: Discussionmentioning

confidence: 99%

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation

Kuo

Rau

et al. 2021

IJMS

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Exosomes secreted by adipose-derived stem cells (ADSCs) enhance angiogenesis and wound healing. However, in clinical settings, wounds may be infected by various bacteria or pathogens. We investigated whether human ADSCs stimulated with lipopolysaccharide (LPS) secrete exosomes (ADSC-LPS-exo) that augment the angiogenesis of human umbilical vein endothelial cells (HUVECs). ExoQuick-TC exosome precipitation solution was used to purify exosomes from human ADSC culture media in the presence or absence of 1 µg/mL LPS treatment for 24 h. The uptake of ADSC-LPS-exo significantly induced the activation of cAMP response element binding protein (CREB), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) signaling pathways and increased the migration of and tube formation in HUVECs. RNA interference with CREB, AP-1, or NF-κB1 significantly reduced the migration of and tube formation in HUVECs treated with ADSC-LPS-exo. An experiment with an antibody array for 25 angiogenesis-related proteins revealed that only interleukin-8 expression was significantly upregulated in HUVECs treated with ADSC-LPS-exo. In addition, proteomic analysis revealed that eukaryotic translation initiation factor 4E, amyloid beta A4 protein, integrin beta-1, and ras-related C3 botulinum toxin substrate 1 may be potential candidates involved in ADSC-LPS-exo-mediated enhanced angiogenesis.

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“…Due to its ability to target eukaryotic translation initiation factor 4E (eIF4E), which plays a critical role in the translation of VEGF and other pro-angiogenic genes, Ribavirin has exhibited strong anticancer activity against various cancers. Studies have found that Ribavirin is active against lung cancer cell lines regardless of molecular and cellular heterogeneity, and it acts on lung cancer cells by inhibiting eIF4E and mTOR signaling pathways, thereby inhibiting eIF4E-mediated protein translation and exerting an anti-angiogenic effect ( 79 ). The cholesterol-lowering drug Pitavastatin can inhibit lung cancer-related EC migration and morphologic changes without affecting adhesion, thus demonstrating a role in inhibiting lung cancer cell growth and angiogenesis.…”

Section: Novel Anti-angiogenesis Strategies In Lung Cancer Treatmentmentioning

confidence: 99%

Novel Angiogenic Regulators and Anti-Angiogenesis Drugs Targeting Angiogenesis Signaling Pathways: Perspectives for Targeting Angiogenesis in Lung Cancer

Lin

Wang

et al. 2022

Front. Oncol.

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Lung cancer growth is dependent on angiogenesis. In recent years, angiogenesis inhibitors have attracted more and more attention as potential lung cancer treatments. Current anti-angiogenic drugs targeting VEGF or receptor tyrosine kinases mainly inhibit tumor growth by reducing angiogenesis and blocking the energy supply of lung cancer cells. However, these drugs have limited efficiency, raising concerns about limited scope of action and mechanisms of patient resistance to existing drugs. Therefore, current basic research on angiogenic regulators has focused more on screening carcinogenic/anticancer genes, miRNAs, lncRNAs, proteins and other biomolecules capable of regulating the expression of specific targets in angiogenesis signaling pathways. In addition, new uses for existing drugs and new drug delivery systems have received increasing attention. In our article, we analyze the application status and research hotspots of angiogenesis inhibitors in lung cancer treatment as a reference for subsequent mechanistic research and drug development.

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Inhibition of eIF4E signaling by ribavirin selectively targets lung cancer and angiogenesis

Cited by 18 publications

References 34 publications

Identification of Diagnostic Markers in Infantile Hemangiomas

Identification of Diagnostic Markers in Infantile Hemangiomas

Increased Angiogenesis by Exosomes Secreted by Adipose-Derived Stem Cells upon Lipopolysaccharide Stimulation

Novel Angiogenic Regulators and Anti-Angiogenesis Drugs Targeting Angiogenesis Signaling Pathways: Perspectives for Targeting Angiogenesis in Lung Cancer

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