Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets

Vivarelli, Silvia; Falzone, Luca; Ligresti, Giovanni; Candido, Saverio; Garozzo, A; Magro, Gaetano; Bonavida, Benjamin; Libra, Massimo

doi:10.3390/ijms21176446

Cited by 8 publications

(15 citation statements)

References 67 publications

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“…In cancer, YY1 plays a controversial role [ 25 , 26 , 27 ]. Regarding LC, YY1 has been seen to work as an oncogene, although the mechanism is still not well defined [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

Vivarelli

Falzone

Grillo

et al. 2022

Cancers

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Lung cancer (LC) represents a global threat, being the tumor with the highest mortality rate. Despite the introduction of novel therapies (e.g., targeted inhibitors, immune-checkpoint inhibitors), relapses are still very frequent. Accordingly, there is an urgent need for reliable predictive biomarkers and therapeutically druggable targets. Yin-Yang 1 (YY1) is a transcription factor that may work either as an oncogene or a tumor suppressor, depending on the genotype and the phenotype of the tumor. The Raf Kinase Inhibitory Protein (RKIP), is a tumor suppressor and immune enhancer often found downregulated in the majority of the examined cancers. In the present report, the role of both YY1 and RKIP in LC is thoroughly explored through the analysis of several deposited RNA and protein expression datasets. The computational analyses revealed that YY1 negatively regulates RKIP expression in LC, as corroborated by the deposited YY1-ChIP-Seq experiments and validated by their robust negative correlation. Additionally, YY1 expression is significantly higher in LC samples compared to normal matching ones, whereas RKIP expression is lower in LC and high in normal matching tissues. These observed differences, unlike many current biomarkers, bear a diagnostic significance, as proven by the ROC analyses. Finally, the survival data support the notion that both YY1 and RKIP might represent strong prognostic biomarkers. Overall, the reported findings indicate that YY1 and RKIP expression levels may play a role in LC as potential biomarkers and therapeutic targets. However, further studies will be necessary to validate the in silico results.

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“…In cancer, YY1 plays a controversial role [ 25 , 26 , 27 ]. Regarding LC, YY1 has been seen to work as an oncogene, although the mechanism is still not well defined [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

Vivarelli

Falzone

Grillo

et al. 2022

Cancers

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“…Studies have found that YY1 is highly expressed in many cancers, participates in the regulation of tumor proliferation and growth, and plays a dual role in inhibiting or promoting tumor progression [ 12 ]. For example, YY1 inhibits tumor proliferation in colon cancer and breast cancer [ 14 ] but promotes tumor growth in melanoma, non-Hodgkin Lymphomas [ 15 ], and prostate cancer [ 12 ]. The expression of YY1 is significantly increased in colon cancer and subjected to O-GlcNAcylation modifications, which increases the stability and transcriptional activity of YY1, thus promoting tumor proliferation [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of Yin-Yang-1 Associates with Proliferation and Glutamine Metabolism in Esophageal Carcinoma

Luo

Chen

Bai

et al. 2022

International Journal of Genomics

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Objective. To investigate the expression of Yin-Yang-1 (YY1) in esophageal carcinoma (ESCA) and its effect on glutamine metabolism in ESCA. Methods. The expression and roles of YY1 in ESCA were investigated using a series of bioinformatics databases and tools. The expression of YY1 between ESCA tissues with the corresponding adjacent tissues was validated using real-time PCR, western blot, and immunohistochemical staining method. Furthermore, the effects of YY1 on ESCC cell proliferation and migration were examined. The correlation between the YY1 and glutamine metabolism was evaluated by western blot. Results. YY1 gene was highly conserved in evolution and upregulated in ESCA tissues and ESCC cell lines (ECA109 and TE-1). In addition, YY1 may affect the level of immune cell infiltration and promote tumor cell immune escape. Functional enrichment analysis found that YY1 involved in many biological processes, such as cell division and glutathione and glutamine metabolism. After siRNA knockdown of YY1 in ECA109 and TE-1, the proliferation and the migration of ECA109 and TE-1 were suppressed. The glutamine consumption and glutamate production were significantly decreased. The protein expression of alanine-, serine-, cysteine-preferring transporter 2 (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLUD1) was significantly downregulated. Conclusion. YY1 is highly expressed in ESCA and may promote glutamine metabolism of ESCC cells, indicating it may be as a diagnostic biomarker for ESCA.

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“…The YY1 gene is 23 kb long and is highly conserved across cells; its translated protein consists of 414 amino acids [ 45 , 46 , 47 ]. Due to its roles in the cell cycle, gene expression, DNA repair, cellular metabolism, differentiation, survival, and apoptosis, YY1 is vital in early developmental processes as well as lifelong regulatory processes [ 48 , 49 , 50 ]. However, it has also been found that YY1 is overexpressed in many types of cancers, specifically in several metastatic cancers [ 51 , 52 , 53 , 54 ].…”

Section: Yy1 Overexpression In Cancer Oncogenic and Immunosuppressive...mentioning

confidence: 99%

Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1

Dillen,

Bui,

Jung

et al. 2024

Cancers

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During the last decade, we have witnessed several milestones in the treatment of various resistant cancers including immunotherapeutic strategies that have proven to be superior to conventional treatment options, such as chemotherapy and radiation. This approach utilizes the host’s immune response, which is triggered by cancer cells expressing tumor-associated antigens or neoantigens. The responsive immune cytotoxic CD8+ T cells specifically target and kill tumor cells, leading to tumor regression and prolongation of survival in some cancers; however, some cancers may exhibit resistance due to the inactivation of anti-tumor CD8+ T cells. One mechanism by which the anti-tumor CD8+ T cells become dysfunctional is through the activation of the inhibitory receptor programmed death-1 (PD-1) by the corresponding tumor cells (or other cells in the tumor microenvironment (TME)) that express the programmed death ligand-1 (PD-L1). Hence, blocking the PD-1/PD-L1 interaction via specific monoclonal antibodies (mAbs) restores the CD8+ T cells’ functions, leading to tumor regression. Accordingly, the Food and Drug Administration (FDA) has approved several checkpoint antibodies which act as immune checkpoint inhibitors. Their clinical use in various resistant cancers, such as metastatic melanoma and non-small-cell lung cancer (NSCLC), has shown significant clinical responses. We have investigated an alternative approach to prevent the expression of PD-L1 on tumor cells, through targeting the oncogenic transcription factor Yin Yang 1 (YY1), a known factor overexpressed in many cancers. We report the regulation of PD-L1 by YY1 at the transcriptional, post-transcriptional, and post-translational levels, resulting in the restoration of CD8+ T cells’ anti-tumor functions. We have performed bioinformatic analyses to further explore the relationship between both YY1 and PD-L1 in cancer and to corroborate these findings. In addition to its regulation of PD-L1, YY1 has several other anti-cancer activities, such as the regulation of proliferation and cell viability, invasion, epithelial–mesenchymal transition (EMT), metastasis, and chemo-immuno-resistance. Thus, targeting YY1 will have a multitude of anti-tumor activities resulting in a significant obliteration of cancer oncogenic activities. Various strategies are proposed to selectively target YY1 in human cancers and present a promising novel therapeutic approach for treating unresponsive cancer phenotypes. These findings underscore the distinct regulatory roles of YY1 and PD-L1 (CD274) in cancer progression and therapeutic response.

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Role of the Transcription Factor Yin Yang 1 and Its Selectively Identified Target Survivin in High-Grade B-Cells Non-Hodgkin Lymphomas: Potential Diagnostic and Therapeutic Targets

Cited by 8 publications

References 67 publications

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

Upregulation of Yin-Yang-1 Associates with Proliferation and Glutamine Metabolism in Esophageal Carcinoma

Regulation of PD-L1 Expression by YY1 in Cancer: Therapeutic Efficacy of Targeting YY1

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