Function of noncoding RNA in regulating cancer cell plasticity DOI Creative Commons

Peter Hyunwuk Her,

Magnus Lam,

Su Zeng

и другие.

Опубликована: Ноя. 12, 2024

Recent advances have brought non-coding RNAs (ncRNAs) into the spotlight, revealing their critical regulatory roles in cancer cell plasticity. ncRNAs, such as microRNAs (miRNAs), transfer (tRNAs), long (lncRNAs) and circular (circRNAs), are now recognized key players cellular processes chromatin remodeling, mRNA stability, translation. This review delves diverse functions of ncRNAs stem cells (CSCs) biology, emphasizing impact on maintaining modulating states. We explore mechanisms by which influence self-renewal differentiation, including establishing pluripotency directing differentiation. In context cancer, pivotal driving like epithelial-mesenchymal transition (EMT), underlies metastasis therapy resistance. By regulating gene expression epigenetic landscapes, sustain dynamic nature CSCs, facilitating tumor growth heterogeneity. The also highlights potential clinical applications biomarkers therapeutic targets. Advances ncRNA detection manipulation opened new avenues for developing diagnostic tools innovative treatments. Liquid biopsies, utilize from biological fluids, provide a minimally invasive approach to monitor dynamics progression. Uncovering intricate networks regulated makes it evident that these molecules play central understanding Insights offer promising strategies targeted therapies, aiming disrupt adaptability improve treatment outcomes.

Язык: Английский

Sequence-Defined DNA Polymers: New Tools for DNA Nanotechnology and Nucleic Acid Therapy DOI
Muhammad Ghufran Rafique, Quentin Laurent, Michael D. Dore

и другие.

Accounts of Chemical Research, Год журнала: 2025, Номер 58(2), С. 177 - 188

Опубликована: Янв. 8, 2025

ConspectusStructural DNA nanotechnology offers a unique self-assembly toolbox to construct soft materials of arbitrary complexity, through bottom-up approaches including origami, brick, wireframe, and tile-based assemblies. This can be expanded by incorporating interactions orthogonal base-pairing such as metal coordination, small molecule hydrogen bonding, π-stacking, fluorophilic interactions, or the hydrophobic effect. These allow for hierarchical long-range organization in supramolecular assemblies DNA-minimal approach: use fewer sequences make complex structures.Here we describe our research group's work integrate these into its Using automated solid phase techniques, synthesized sequence-defined polymers (SDPs) featuring wide range functional groups, achieving high yields process. SDPs assemble not only isotropic spherical morphologies─such nucleic acids (SNAs)─but also anisotropic nanostructures 1D nanofibers 2D nanosheets. Our structural molecular modeling studies revealed new insights intermolecular chain packing intramolecular folding, influenced phosphodiester positioning SDP sequence. paradigms, created hierarchical, developed systems exhibiting polymorphism chiroptical behavior dependent on We could precisely control size nanofiber via nucleation-growth polymerization create compartmentalized capable precise surface functionalization.The exquisite over sequence, composition, length allowed us combine with wireframe prisms, nanotubes, cubes hybrid, stimuli-responsive emergent modes. The spatial enabled their nanoreactors chemical transformations several ways: hybridization reaction within SNA coronas, conjugation cores, "printing" approach nanoscale information transfer creation "DNA-printed" polymer particles.We have employed toward biological therapeutic applications. demonstrated that SNAs serve both extrinsic intrinsic platforms, improved cellular internalization biodistribution profiles, excellent gene silencing activities. dendrons, high-affinity highly specific oligonucleotide binding human serum albumin was demonstrated. structures showed an increased stability nuclease degradation, reduced nonspecific uptake, no toxicity even at concentrations, beyond liver, resulting unprecedented activity various tissues.Control sequence has thus presented polymeric building block form SDP, which combines diversity programmability DNA. By linking assembly languages, discovered rules, nanostructures, utility Developing this further will open avenues fields nanomaterials, acid therapeutics, well copolymer self-assembly.

Язык: Английский

Процитировано

1
Bioanalytical Assays for Oligonucleotide Therapeutics: Adding Antibody-Based Immunoassays to the Toolbox as an Orthogonal Approach to LC-MS/MS and Ligand Binding Assays DOI
David P. Chimento, Amy Anderson,

Inês Fial

и другие.

Nucleic Acid Therapeutics, Год журнала: 2025, Номер 35(1), С. 6 - 15

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
TAMing Gliomas: Unraveling the Roles of Iba1 and CD163 in Glioblastoma DOI Open Access

Haneya Fuse,

Yuqi Zheng, Islam Alzoubi

и другие.

Cancers, Год журнала: 2025, Номер 17(9), С. 1457 - 1457

Опубликована: Апрель 26, 2025

Gliomas, the most common type of primary brain tumor, are a significant cause morbidity and mortality worldwide. Glioblastoma, highly malignant subtype, is particularly common, aggressive, resistant to treatment. The tumor microenvironment (TME) gliomas, especially glioblastomas, characterized by distinct presence tumor-associated macrophages (TAMs), which densely infiltrate hallmark these tumors. This macrophage population comprises both tissue-resident microglia as well derived from walls blood vessels stream. Ionized calcium-binding adapter molecule 1 (Iba1) CD163 established cellular markers that enable identification functional characterization cells within TME. review provides an in-depth examination roles Iba1 in with focus on TAM activation, migration, immunomodulatory functions. Additionally, we will discuss how recent advances AI-enhanced cell visualization techniques have begun transform analysis TAMs, promising unprecedented precision their providing new insights into appear unique shared glioma pathobiology, potential be targeted through different molecular mechanisms. We therapeutic based available preclinical (experimental) clinical (human tissue-based) evidence.

Язык: Английский

Процитировано

0
Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in MGMT -methylated glioblastoma DOI
Xinyi Liao, Shuxia Zhang, Xincheng Li

и другие.

Science Translational Medicine, Год журнала: 2024, Номер 16(767)

Опубликована: Окт. 2, 2024

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance cellular physiological function and survival remain unclear. Here, we showed that in MGMT promoter–methylated glioblastoma (GBM), RNA helicase DEAD-box 46 (DDX46) is phosphorylated by temozolomide (TMZ)–activated checkpoint kinase 1 (CHK1), resulting a dense-to-loose conformational change an increase DDX46 activity. DDX46-mediated tertiary LINC01956 exposes binding motifs to 3′ untranslated region O 6 -methylguanine DNA methyltransferase ( ). This accelerates recruitment mRNA export machinery transportation from nucleus cytoplasm, leading increased abundance TMZ resistance. Using patient-derived xenograft (PDX) tumor organoid models, found treatment with CHK1 inhibitor SRA737abolishes TMZ-induced subsequent up-regulation, resensitizing TMZ-resistant GBM TMZ. In conclusion, these findings highlight mechanism temozolomide-induced may represent potential therapeutic strategy patients GBM.

Язык: Английский

Процитировано

1
Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system DOI Creative Commons
Alexander G. Sorets,

Katrina Schwensen,

Nora Francini

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 10, 2024

Short-interfering RNA (siRNA) has gained significant interest for treatment of neurological diseases by providing the capacity to achieve sustained inhibition nearly any gene target. Yet, efficacious drug delivery throughout deep brain structures CNS remains a considerable hurdle intrathecally administered therapeutics. We herein describe an albumin-binding lipid-siRNA conjugate that transports along meningeal and perivascular CSF pathways, leading broad dispersion parenchyma. provide detailed examination temporal kinetics silencing, highlighting potent knockdown up five months from single injection without detectable toxicity. Single-cell sequencing further demonstrates silencing activity across diverse cell populations in parenchyma at borders, which may new avenues disease-modifying therapies.

Язык: Английский

Процитировано

0
Function of noncoding RNA in regulating cancer cell plasticity DOI Creative Commons

Peter Hyunwuk Her,

Magnus Lam,

Su Zeng

и другие.

Опубликована: Ноя. 12, 2024

Recent advances have brought non-coding RNAs (ncRNAs) into the spotlight, revealing their critical regulatory roles in cancer cell plasticity. ncRNAs, such as microRNAs (miRNAs), transfer (tRNAs), long (lncRNAs) and circular (circRNAs), are now recognized key players cellular processes chromatin remodeling, mRNA stability, translation. This review delves diverse functions of ncRNAs stem cells (CSCs) biology, emphasizing impact on maintaining modulating states. We explore mechanisms by which influence self-renewal differentiation, including establishing pluripotency directing differentiation. In context cancer, pivotal driving like epithelial-mesenchymal transition (EMT), underlies metastasis therapy resistance. By regulating gene expression epigenetic landscapes, sustain dynamic nature CSCs, facilitating tumor growth heterogeneity. The also highlights potential clinical applications biomarkers therapeutic targets. Advances ncRNA detection manipulation opened new avenues for developing diagnostic tools innovative treatments. Liquid biopsies, utilize from biological fluids, provide a minimally invasive approach to monitor dynamics progression. Uncovering intricate networks regulated makes it evident that these molecules play central understanding Insights offer promising strategies targeted therapies, aiming disrupt adaptability improve treatment outcomes.

Язык: Английский

Процитировано

0