The regulation of <scp>N6</scp>‐methyladenosine modification in <scp>PD‐L1</scp>‐induced anti‐tumor immunity

Yu, Wei; Lin, Jinti; Yu, Tao; Lou, Jianan; Chao, Qian; Xu, Ankai; Liu, Bing; Tao, Huimin; Jin, Liu

doi:10.1111/imcb.12620

Cited by 3 publications

(2 citation statements)

References 108 publications

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“…N6-methyladenosine (m6A) is the most abundant internal modi cation in mRNAs and it is a reversible and dynamic process that regulated by "Writer," "Eraser," and "Reader" proteins [23]. The PD-L1 mRNA is also modi ed by m6A and its regulators were extensively studied [24,25]. The PD-L1 mRNA level is closely associated with ALKBH5, an eraser of m6A [25].…”

Section: Discussionmentioning

confidence: 99%

The 3’ non-coding sequence negatively regulates PD-L1 expression and its regulators are systematically identified in pan-cancer

Chen

Wang

et al. 2023

Preprint

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Objective Comparing to the coding sequences (CDS), the 3’-untranslated region (3’-UTR) of PD-L1 is extremely longer but its role and regulators are less explored.Methods The whole 3’-UTR region was deleted by CRISPR-Cas9. Prognostic analysis was performed using online tools. Immune infiltration analysis was performed using Timer and Xcell package. Immunotherapy response prediction and cox regression were performed using R software. MicroRNA network analysis was conducted by Cytoscape software.Results The level of PD-L1 was dramatically and significantly up-regulated in 3’-UTR deficient cells. Furthermore, we found a panel of 43 RNA binding proteins (RBPs) that correlated with PD-L1 in a majority of cancer cell lines and tumor tissues. Among them, PARP14 is widely associated with immune checkpoints, tumor microenvironment and immune infiltrating cells in various cancer types. We also identified 38 MicroRNA that associated with PD-L1 across cancers. The miR-3139, miR-4761 and miR-15a-5p are significantly associated with PD-L1 in most of cancer types. Finally, we revealed 21 m6A regulators that have a strong correlation with PD-L1. More importantly, by combing the identified RBPs and m6A regulators, we established a predictive immune signature including RBMS1, QKI, YTHDC1, ZC3HAV1, RBM38 and PPARGC1B to predict the responsiveness of cancer patients upon receiving immune checkpoint blockade.Conclusions We demonstrated the critical role of 3’-UTR in the regulation of PD-L1 and uncovered a large number of potential PD-L1 regulators in pan-cancer. The generated biomarker signature has power to predict patient’s prognosis, but along with the potential PD-L1 regulators should be further biologically investigated.

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Section: Discussionmentioning

confidence: 99%

The 3’ non-coding sequence negatively regulates PD-L1 expression and its regulators are systematically identified in pan-cancer

Chen

Wang

et al. 2023

Preprint

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“…This modification is reversible and dynamically regulated by proteins known as “Writer”, “Eraser”, and “Reader” [ 23 ]. The PD-L1 mRNA is also modified by m6A, and its regulators have been extensively studied [ 24 , 25 ]. The level of PD-L1 mRNA is closely linked with ALKBH5, an Eraser of m6A modifications [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

The 3′ Non-Coding Sequence Negatively Regulates PD-L1 Expression, and Its Regulators Are Systematically Identified in Pan-Cancer

Chen

Zheng

et al. 2023

Genes

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The 3′-untranslated region (3′-UTR) of PD-L1 is significantly longer than the coding sequences (CDSs). However, its role and regulators have been little studied. We deleted whole 3′-UTR region by CRISPR-Cas9. Prognostic analysis was performed using online tools. Immune infiltration analysis was performed using the Timer and Xcell packages. Immunotherapy response prediction and Cox regression was performed using the R software. MicroRNA network analysis was conducted by the Cytoscape software. The level of PD-L1 was significantly and dramatically up-regulated in cells after deleting the 3′-UTR. Additionally, we discovered a panel of 43 RNA-binding proteins (RBPs) whose expression correlates with PD-L1 in the majority of cancer cell lines and tumor tissues. Among these RBPs, PARP14 is widely associated with immune checkpoints, the tumor microenvironment, and immune-infiltrating cells in various cancer types. We also identified 38 microRNAs whose individual expressions are associated with PD-L1 across different cancers. Notably, miR-3139, miR-4761, and miR-15a-5p showed significant associations with PD-L1 in most cancer types. Furthermore, we revealed 21 m6A regulators that strongly correlate with PD-L1. Importantly, by combining the identified RBP and m6A regulators, we established an immune signature consisting of RBMS1, QKI, ZC3HAV1, and RBM38. This signature can be used to predict the responsiveness of cancer patients to immune checkpoint blockade treatment. We demonstrated the critical role of the 3′-UTR in the regulation of PD-L1 and identified a significant number of potential PD-L1 regulators across various types of cancer. The biomarker signature generated from our findings shows promise in predicting patient prognosis. However, further biological investigation is necessary to explore the potential of these PD-L1 regulators.

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IGF2BP3 boosts lactate generation to accelerate gastric cancer immune evasion

Lin,

Luo

2024

Apoptosis

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The regulation of N6‐methyladenosine modification in PD‐L1‐induced anti‐tumor immunity

Cited by 3 publications

References 108 publications

The 3’ non-coding sequence negatively regulates PD-L1 expression and its regulators are systematically identified in pan-cancer

The 3’ non-coding sequence negatively regulates PD-L1 expression and its regulators are systematically identified in pan-cancer

The 3′ Non-Coding Sequence Negatively Regulates PD-L1 Expression, and Its Regulators Are Systematically Identified in Pan-Cancer

IGF2BP3 boosts lactate generation to accelerate gastric cancer immune evasion

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