N6-methyladenosine methyltransferases: functions, regulation, and clinical potential

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: July 27, 2021

Abstract N6-methyladenosine (m6A) has emerged as an abundant modification throughout the transcriptome with widespread functions in protein-coding and noncoding RNAs. It affects fates of modified RNAs, including their stability, splicing, and/or translation, thus plays important roles posttranscriptional regulation. To date, m6A methyltransferases have been reported to execute deposition on distinct RNAs by own or forming different complexes additional partner proteins. In this review, we summarize function these regulating key genes pathways cancer biology. We also highlight progress use mediating therapy resistance, chemotherapy, targeted therapy, immunotherapy radiotherapy. Finally, discuss current approaches clinical potential methyltransferase-targeting strategies.

Language: Английский

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SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial–mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(5)

Published: May 5, 2021

Abstract Sex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer cells (CSCs) properties, fuels tumor initiation, contributes to aggressiveness. Our previous study has demonstrated the oncogenic role SOX2 in colorectal (CRC). In this study, we sought elucidate underlying mechanisms. Cell function experiments were performed detect chemoresistance, proliferation, stemness, migration, invasion vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, immunofluorescence explore regulation ABCC2, β-catenin, Beclin1 by SOX2. The carcinogenic SOX2-β-catenin/Beclin1-ABCC2 axis vivo was analyzed CRC tissues xenograft models. Here, reported that sustained chemoresistance transcriptional activation ABCC2 expression. Suppressing either β-catenin or autophagy signaling curbed SOX2-driven epithelial–mesenchymal transition (EMT). Mechanistically, combined with increased its nuclear expression activity. Transcriptional consequently activating inducing malignant phenotype. Furthermore, overexpression facilitated clinical analyses showed high positively correlated associated poor prognosis patients. Finally, models revealed inhibition restrained growth vivo. Conclusively, novel mechanism which SOX2-β-catenin/Beclin1/autophagy regulates EMT CRC. findings provide insights into carcinogenesis may help develop potential therapeutic candidates for

Language: Английский

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Insights on functionalized carbon nanotubes for cancer theranostics

Journal of Nanobiotechnology, Journal Year: 2021, Volume and Issue: 19(1)

Published: Dec. 16, 2021

Abstract Despite the exciting breakthroughs in medical technology, cancer still accounts for one of principle triggers death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement therapy with gigantic application potential because their ability achieving precise controlled drug release, elevating solubility reducing adverse effects. Carbon nanotubes (CNTs), most promising carbon-related nanomaterials, have already achieved much success biomedical field. Due excellent optical property, thermal electronic conductivity, easy functionalization high loading capacity, CNTs can be applied a multifunctional way treatment diagnosis. In this review, we will give overview recent progress CNT-based delivery systems theranostics, which emphasizes targetability intracellular components tumor cells extracellular elements microenvironment. Moreover, detailed introduction on how penetrate inside reach sites action achieve effects, as well diagnostic applications highlighted. Graphic

Language: Английский

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Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 21, 2023

Abstract Ongoing research has revealed that the existence of cancer stem cells (CSCs) is one biggest obstacles in current therapy. CSCs make an influential function tumor progression, recurrence and chemoresistance due to their typical stemness characteristics. are preferentially distributed niches, those niche sites exhibit characteristics microenvironment (TME). The complex interactions between TME illustrate these synergistic effects. phenotypic heterogeneity within spatial with surrounding led increased therapeutic challenges. interact immune protect themselves against clearance by exploiting immunosuppressive multiple checkpoint molecules. also can surveillance excreting extracellular vesicles (EVs), growth factors, metabolites cytokines into TME, thereby modulating composition TME. Therefore, being considered for development anti-tumor agents. We discuss here molecular mechanisms comprehensively review interplay system. Thus, studies on this topic seem provide novel ideas reinvigorating approaches cancer.

Language: Английский

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Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 80(1), P. 82 - 98

Published: Oct. 12, 2023

Language: Английский

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Cancer stem cells and niches: challenges in immunotherapy resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 25, 2025

Cancer stem cells (CSCs) are central to tumor progression, metastasis, immune evasion, and therapeutic resistance. Characterized by remarkable self-renewal adaptability, CSCs can transition dynamically between stem-like differentiated states in response external stimuli, a process termed "CSC plasticity." This adaptability underpins their resilience therapies, including checkpoint inhibitors adoptive cell therapies (ACT). Beyond intrinsic properties, reside specialized microenvironment—the CSC niche—which provides immune-privileged protection, sustains stemness, fosters suppression. review highlights the critical role of niche driving immunotherapy resistance, emphasizing need for integrative approaches overcome these challenges.

Language: Английский

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Tumor‐derived exosomal BCYRN1 activates WNT5A/VEGF‐C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer

Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(7)

Published: July 1, 2021

Language: Английский

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Chemotoxicity-induced exosomal lncFERO regulates ferroptosis and stemness in gastric cancer stem cells

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(12)

Published: Nov. 29, 2021

Abstract Cancer stem cells (CSCs) are an important cause of tumor recurrence and drug resistance. As a new type cell death that relies on iron ions is strictly regulated by intracellular extracellular signals, the role ferroptosis in deserves extensive attention. Mass spectrum was applied to screen for ferroptosis-related proteins gastric cancer (GC). Sphere-formation assay used estimate stemness (GCSCs). Exosomal lnc-ENDOG-1:1 (lncFERO) isolated ultracentrifugation. Ferroptosis induced erastin assessed detecting lipid ROS, mitochondrial membrane potential, death. Furthermore, series functional vitro vivo experiments were conducted evaluate effects lncFERO regulating chemosensitivity GCSCs. Here, we showed stearoyl-CoA-desaturase (SCD1) played key metabolism Importantly, exosomal (exo-lncFERO) derived from GC demonstrated promote SCD1 expression directly interacting with mRNA recruiting heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), which resulted dysregulation PUFA levels suppression Moreover, found hnRNPA1 also involved packing into exosomes cells, both data suggested chemotoxicity secretion upregulating expression, leading enhanced acquired chemo-resistance. All these suggest exo-lncFERO controls GCSC tumorigenic properties through suppressing ferroptosis, targeting exo-lncFERO/hnRNPA1/SCD1 axis combined chemotherapy could be promising CSC-based strategy treatment GC.

Language: Английский

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Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

Biomarker Research, Journal Year: 2021, Volume and Issue: 9(1)

Published: March 1, 2021

Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms evading surveillance immunotherapy response targeting special components.Using a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the bone marrow (BM) samples from 16 AML patients 4 healthy donors, but not blasts.We observed significant difference between normal BM cells. Here, defined diversity dendritic cells (DC) macrophages different patients. We also identified several unique types including T helper 17 (TH17)-like intermediate population, cytotoxic CD4+ subset, cell: erythrocyte complexes, activated regulatory (Treg), CD8+ memory-like subset. Emerging remodels powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional effectors, expending immune-activated types, promoting formation suppressive subsets.Our results provide comprehensive census, which can help select pinpoint targeted drug predict efficacy immunotherapy.

Language: Английский

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MiRNA-mediated EMT and CSCs in cancer chemoresistance

Experimental Hematology and Oncology, Journal Year: 2021, Volume and Issue: 10(1)

Published: Feb. 12, 2021

Abstract Cancer stem cells (CSCs) are a small group of cancer cells, which contribute to tumorigenesis and progression. undergoing epithelial-to-mesenchymal transition (EMT) acquire the chemoresistant ability, is regarded as an important feature CSCs. Thus, there emerges opinion that generation CSCs considered be driven by EMT. In this complex process, microRNAs (miRNAs) found play key role. order overcome drug resistance, inhibiting EMT well phenotype seem feasible. Thereinto, regulating EMT- or CSCs-associated miRNAs crucial approach. Herein, we conduct review elaborate on complicated interplay between in chemoresistance, modulated miRNAs. addition, elucidate therapeutic strategy resistance through targeting

Language: Английский

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