YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance

Kwiatkowska, Dominika; Mazur, Ewelina; Reich, Adam

doi:10.3389/fonc.2022.856963

Cited by 9 publications

(13 citation statements)

References 72 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MiR-3666/KLF7 axis, as the downstream target of KCNQ1OT1, regulate tumor growth ( Huang et al, 2021 ). The zinc finger protein YY1 belongs to the GLI-Kruppel class and is widely distributed throughout the human body ( Kwiatkowska et al, 2022 ). Early growth response protein-1 (EGR1) encodes a zinc finger protein of the EGR family, which is involved in transcriptional regulation ( Wang et al, 2021c ).…”

Section: Discussionmentioning

confidence: 99%

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients

Han

Zhao²,

Wang³

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

The most common primary malignant bone sarcoma is Osteogenic sarcoma (OS) which has a bimodal age distribution. Unfortunately, the treatment of OS was less effective for elderly patients than for younger ones. The study aimed to explore a new microRNA (miRNA) which can bind to combining engineered exosomes for treatment of older OS patients. Based on GSE65071 and miRNet 2.0, two up-regulated miRNAs (miR-328, miR-107) and seven down-regulated miRNAs (miR-133b, miR-206, miR-1-3p, miR-133a, miR-449a, miR-181daysay, miR-134) were selected. Next, we used FunRich software to predict the up-stream transcription factors (TFs) of differentially expressed miRNAs (DE-miRNAs). By comparing target genes predicted from DE-miRNAs with differentially expressed genes, we identified 12 down-regulated and 310 up-regulated mRNAs. For KEGG analysis, the most enriched KEGG pathway was Cell cycle, Spliceosome, and Protein digestion and absorption. By using protein-protein interactions network, topological analysis algorithm and GEPIA database, miR-449a /CCNB1 axis was identified. Experiments in vitro were conducted to confirm the results too. MiRNA-449a is down-regulated in osteosarcoma and suppresses cell proliferation by targeting CCNB1. Our findings not only reveal a novel mechanism of miR-449a /CCNB1 in OS but also had laid the groundwork for further investigation and analysis in the field of exosome engineering.

show abstract

Section: Discussionmentioning

confidence: 99%

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients

Han

Zhao²,

Wang³

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…The effects of T-cell exhaustion manifest in decreased proliferation, increased expression of inhibitory checkpoint molecules such as PD-1, impaired production of type I cytokines, and reduced ability to kill antigenic targets [ 101 , 102 , 103 ]. The inactivation of PD-1-expressing CD8 + T cells by PD-L1 inhibits tumor-infiltrating CD4 + /CD8 + T cells (CD4 + /CD8 + TILs) and leads to a decrease in cytokines including tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 2 (IL-2), allowing cancer cells to escape the immune reaction [ 104 , 105 , 106 , 107 ]. In a study by Baitsch et al [ 101 ], melanoma samples were found to have a majority of their tumor-infiltrating lymphocytes (TILs) exhausted from PD-1 compared to normal T-cell function in non-cancerous skin cells [ 101 ].…”

Section: Role Of the Pd-1/pd-l1 Interaction In The Inactivation Of An...mentioning

confidence: 99%

“…In a study by Baitsch et al [ 101 ], melanoma samples were found to have a majority of their tumor-infiltrating lymphocytes (TILs) exhausted from PD-1 compared to normal T-cell function in non-cancerous skin cells [ 101 ]. It was concluded that upregulation of PD-L1 expression is a mechanism for tumor cells to defend themselves from cell death by cytotoxic T cells [ 104 , 105 , 106 , 107 ] ( Figure 2 ).…”

Section: Role Of the Pd-1/pd-l1 Interaction In The Inactivation Of An...mentioning

confidence: 99%

“…T-cell exhaustion also plays a role in the progression of several cancer types and is a promising target for novel immunotherapies [ 101 , 201 , 208 ]. Furthermore, Balkhi et al [ 102 , 107 ] found that in human melanoma cells, the activation of the p38/mitogen-activated protein kinase (MAPK)/jun N-terminal kinase (JNK) pathway leads to increased YY1 expression. YY1 then binds to the PD-1 promoter, ultimately leading to transcriptional upregulation.…”

Section: Implications Of Yy1-mediated Regulation Of Pd-1/pd-l1 Axis I...mentioning

confidence: 99%

See 1 more Smart Citation

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

Dillen,

Bui,

Jung

et al. 2024

Cancers

View full text Add to dashboard Cite

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.

show abstract

“…Programmed death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) are the most common immune checkpoint receptors expressed on the surface of T lymphocytes ( 60 ). YY1 has been shown to positively regulate immune checkpoint receptors such as PD1 and CTLA-4 ( 61 ), and YY1 was upregulated in PD1-positive T cells infiltrating lymphocytes in melanoma tumors and directly regulated the expression of PD1 and LAG3 by binding to the promoter region ( 62 , 63 ). PD-1 is a critical receptor expressed on activated T cells that inhibits T cell-mediated immune responses upon binding to its ligand programmed cell death ligand 1 (PD-L1) ( 64 ).…”

Section: Role Of Yy1 In the Tumor Microenvironmentmentioning

confidence: 99%

Dissecting the roles and clinical potential of YY1 in the tumor microenvironment

Wei

Xue

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Yin-Yang 1 (YY1) is a member of the GLI-Kruppel family of zinc finger proteins and plays a vital dual biological role in cancer as an oncogene or a tumor suppressor during tumorigenesis and tumor progression. The tumor microenvironment (TME) is identified as the “soil” of tumor that has a critical role in both tumor growth and metastasis. Many studies have found that YY1 is closely related to the remodeling and regulation of the TME. Herein, we reviewed the expression pattern of YY1 in tumors and summarized the function and mechanism of YY1 in regulating tumor angiogenesis, immune and metabolism. In addition, we discussed the potential value of YY1 in tumor diagnosis and treatment and provided a novel molecular strategy for the clinical diagnosis and treatment of tumors.

show abstract

YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance

Cited by 9 publications

References 72 publications

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients

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

Dissecting the roles and clinical potential of YY1 in the tumor microenvironment

Contact Info

Product

Resources

About