Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis

Wang, Lina; Zhu, Lefan; Liang, C.; Huang, Xiang; Liu, Ziqin; Huo, Jihui; Zhang, Ying; Zhang, Yifan; Chen, Lili; Xu, Hui; Li, Xiaoxing; Xu, Lixia; Kuang, Ming; Yu, Jun; Yu, Jun

doi:10.1016/j.jhep.2023.06.021

Cited by 26 publications

(9 citation statements)

References 29 publications

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“…The M6A regulator has the ability to target hundreds of M6A-modified transcripts, including oncogenes and antioncogenes [ 7 , 26 ]. Moreover, the ultimate fate of m6A-modified mRNAs critically depends on the m6A reader [ 32 , 33 ]. We have analyzed the combined effects of all m6A regulators in COAD and READ, and cannot rule out the oncogenic effects of individual m6A regulators in COAD and READ.…”

Section: Discussionmentioning

confidence: 99%

Modification patterns and metabolic characteristics of m6A regulators in digestive tract tumors

He,

Hu,

Chen

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Modification patterns and metabolic characteristics of m6A regulators in digestive tract tumors

He,

Hu,

Chen

et al. 2024

Heliyon

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“… 47 They delivered nanovesicles containing siRNA to Yes-associated protein 1 (YAP), a key downstream transcriptional co-activator of Hippo signaling, resulting in tumor regression through directing hepatocyte differentiation to normal hepatocyte-like cells. Other groups have also delivered nanoliposomes containing siRNAs targeting PD-L1, 48 T cell immunoglobulin mucin-3 49 (Tim-3; immune checkpoint molecule), vascular endothelial growth factor 50 (VEGF; angiogenic factor), alpha-fetoprotein 51 (AFP; biomarker for HCC), cyclo-oxygenase-2 52 (COX-2; important for prostaglandin synthesis in inflammatory processes), hypoxia inducible factor 1 subunit alpha 53 (HIF1a), or RNA N 6 − methyladenosine (m 6 A) reader protein YTHDF1 54 either alone or in combination with chemotherapeutics. Moreover, miRNAs can be packaged into nanoliposomes to target specific cellular pathways.…”

Section: Synthetic Lipid Nanovesicle Drug Delivery Platforms For Hccmentioning

confidence: 99%

Lipid Nanovesicle Platforms for Hepatocellular Carcinoma Precision Medicine Therapeutics: Progress and Perspectives

Lehrich,

Delgado

2024

Organogenesis

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality globally. HCC is highly heterogenous with diverse etiologies leading to different driver mutations potentiating unique tumor immune microenvironments. Current therapeutic options, including immune checkpoint inhibitors and combinations, have achieved limited objective response rates for the majority of patients. Thus, a precision medicine approach is needed to tailor specific treatment options for molecular subsets of HCC patients. Lipid nanovesicle platforms, either liposome- (synthetic) or extracellular vesicle (natural)-derived present are improved drug delivery vehicles which may be modified to contain specific cargos for targeting specific tumor sites, with a natural affinity for liver with limited toxicity. This mini-review provides updates on the applications of novel lipid nanovesicle-based therapeutics for HCC precision medicine and the challenges associated with translating this therapeutic subclass from preclinical models to the clinic.

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“…This subsequently triggers the infiltration of myeloid-derived suppressor cells (MDSCs) and inhibits the cytotoxic function of CD8+ T cells against tumor cells. Wang’s findings suggest that combining YTHDF1 targeting inhibition with ICI significantly enhances the therapeutic efficacy of ICI therapy [ 108 ]. In Bao’s study on colorectal cancer, similar findings were observed.…”

Section: Ythdf1 and Cancer Therapymentioning

confidence: 99%

“…It is worth noting that the high expression of CD47 within sEVs enhances the phagocytic activity of tumor-associated macrophages, further enhancing the therapeutic efficacy [ 118 ]. Wang utilized an FDA-approved LNP formulation to design LNP-siRNA drugs targeting YTHDF1, directly silencing its expression and thereby achieving the inhibition of cancer progression [ 108 ]. Bao developed a nanoparticle-based delivery system, specifically vesicular nanoparticle (VNP), to directly target and silence YTHDF1.…”

Section: Ythdf1 and Cancer Therapymentioning

confidence: 99%

YTHDF1 in Tumor Cell Metabolism: An Updated Review

Rong,

Wang,

Wang

et al. 2023

Molecules

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With the advancement of research on m6A-related mechanisms in recent years, the YTHDF protein family within m6A readers has garnered significant attention. Among them, YTHDF1 serves as a pivotal member, playing a crucial role in protein translation, tumor proliferation, metabolic reprogramming of various tumor cells, and immune evasion. In addition, YTHDF1 also exerts regulatory effects on tumors through multiple signaling pathways, and numerous studies have confirmed its ability to assist in the reprogramming of the tumor cell-related metabolic processes. The focus of research on YTHDF1 has shifted in recent years from its m6A-recognition and -modification function to the molecular mechanisms by which it regulates tumor progression, particularly by exploring the regulatory factors that interact with YTHDF1 upstream and downstream. In this review, we elucidate the latest signaling pathway mechanisms of YTHDF1 in various tumor cells, with a special emphasis on its distinctive characteristics in tumor cell metabolic reprogramming. Furthermore, we summarize the latest pathological and physiological processes involving YTHDF1 in tumor cells, and analyze potential therapeutic approaches that utilize YTHDF1. We believe that YTHDF1 represents a highly promising target for future tumor treatments and a novel tumor biomarker.

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Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis

Cited by 26 publications

References 29 publications

Modification patterns and metabolic characteristics of m6A regulators in digestive tract tumors

Modification patterns and metabolic characteristics of m6A regulators in digestive tract tumors

Lipid Nanovesicle Platforms for Hepatocellular Carcinoma Precision Medicine Therapeutics: Progress and Perspectives

YTHDF1 in Tumor Cell Metabolism: An Updated Review

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