Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer

Kamiya, Hajime; Komatsu, Shuhei; Takashima, Yusuke; Ishida, Ryo; Arakawa, Hiroshi; Nishibeppu, Keiji; Kiuchi, Jun; Imamura, Taisuke; Ohashi, Takuma; Shimizu, Hiroki; Arita, Tomohiro; Konishi, Hirotaka; Shiozaki, Atsushi; Kubota, Takeshi; Fujiwara, Hitoshi; Yagyu, Shigeki; Iehara, Tomoko; Otsuji, Eigo

doi:10.1038/s41416-023-02532-3

Cited by 3 publications

(2 citation statements)

References 45 publications

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“…As well, Overexpression of miR-5193 in GC cells leads to reduced expression of PD-L1, which enhances the anti-tumor activity of T cells. This indicates that targeting low levels of miR-5193 in the bloodstream through nucleic acid immunotherapy could be a potential treatment for GC [ 136 ].…”

Section: Micrornas: Bridging the Gap Between Gene Regulation Immune C...mentioning

confidence: 99%

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Zabeti Touchaei,

Vahidi

2024

Cancer Cell Int

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Immunotherapy has revolutionized cancer treatment by harnessing the power of the immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cancer cells. Two key ICIs target the PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor programmed death 1 (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While ICIs have demonstrated remarkable efficacy in various malignancies, only a subset of patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, play a crucial role in modulating immune checkpoints, including PD-1/PD-L1 and CTLA-4. This review summarizes the latest advancements in immunotherapy, highlighting the therapeutic potential of targeting PD-1/PD-L1 and CTLA-4 immune checkpoints and the regulatory role of miRNAs in modulating these pathways. Consequently, understanding the complex interplay between miRNAs and immune checkpoints is essential for developing more effective and personalized immunotherapy strategies for cancer treatment. Graphical Abstract

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Section: Micrornas: Bridging the Gap Between Gene Regulation Immune C...mentioning

confidence: 99%

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Zabeti Touchaei,

Vahidi

2024

Cancer Cell Int

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“…The results of test-scale and large-scale analyses showed that patients with GC had considerably lower plasma levels of miR-5193 than healthy volunteers (HVs). Reduced blood concentrations of miR-5193 are linked to the worsening of GC and its course, and patients with GC may benefit from nucleic acid immunotherapy [ 65 ].…”

Section: Other Factorsmentioning

confidence: 99%

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update

Bintintan,

Burz,

Pintea

et al. 2024

Diagnostics

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Many studies on gastric cancer treatment have identified predictors of immunotherapy benefits. This article provides an update on the major developments in research related to predictive factors of immunotherapy for gastric cancer. We used the search term “predictive factors, immunotherapy, gastric cancer” to find the most current publications in the PubMed database related to predictive factors of immunotherapy in gastric cancer. Programmed cell death, genetic, and immunological factors are the main study topics of immunotherapy’s predictive factors in gastric cancer. Other preventive factors for immunotherapy in gastric cancer were also found, including clinical factors, tumor microenvironment factors, imaging factors, and extracellular factors. Since there is currently no effective treatment for gastric cancer, we strongly propose that these studies be prioritized.

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Circ_0027791 contributes to the growth and immune evasion of hepatocellular carcinoma via the miR‐496/programmed cell death ligand 1 axis in an m6A‐dependent manner

Yu,

Fang,

Fang

et al. 2024

Environmental Toxicology

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Emerging evidence indicates the critical roles of circular RNAs in the development of multiple cancers, containing hepatocellular carcinoma (HCC). Herein, our present research reported the biological function and mechanism of circ_0027791 in HCC progression. Circ_0027791, microRNA‐496 (miR‐496), programmed cell death ligand 1 (PDL1), and methyltransferase‐like 3 (METTL3) levels were detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell viability, proliferation, invasion, and sphere formation ability were detected using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, 5‐ethynyl‐2′‐deoxyuridine, transwell, and sphere formation assays. Macrophage polarization was detected using flow cytometry assay. To understand the role of circ_0027791 during the immune escape, HCC cells were cocultured with peripheral blood mononuclear cells or cytokine‐induced killer (CIK) cells in vitro. A xenograft mouse model was applied to assess the function of circ_0027791 in vivo. After prediction using circinteractome and miRDB, the binding between miR‐496 and circ_0027791 or PDL1 was validated based on a dual‐luciferase reporter assay. Interaction between METTL3 and circ_0027791 was determined using methylated RNA immunoprecipitation (MeRIP)‐qPCR, RIP‐qPCR, and RNA pull‐down assays. Circ_0027791, PDL1, and METTL3 expression were upregulated, and miR‐496 was decreased in HCC patients and cells. Moreover, circ_0027791 knockdown might repress proliferation, invasion, sphere formation, M2 macrophage polarization, and antitumor immune response. Circ_0027791 knockdown repressed HCC tumor growth in vivo. In mechanism, circ_0027791 functioned as a sponge for miR‐496 to increase PDL1 expression. In addition, METTL3 mediated the m6A methylation of circ_0027791 and stabilized its expression. METTL3‐induced circ_0027791 facilitated HCC cell progression partly regulating the miR‐496/PDL1 axis, which provided a new prognostic and therapeutic marker for HCC.

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Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer

Cited by 3 publications

References 45 publications

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Predictive Factors of Immunotherapy in Gastric Cancer: A 2024 Update

Circ_0027791 contributes to the growth and immune evasion of hepatocellular carcinoma via the miR‐496/programmed cell death ligand 1 axis in an m6A‐dependent manner

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