METTL3‐stabilized super enhancers‐lncRNA SUCLG2‐AS1 mediates the formation of a long‐range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma

Clinical and Translational Medicine, Год журнала: 2023, Номер 13(9)

Опубликована: Сен. 1, 2023

Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as super-lncRNA, causes the activity SE to be dysregulated.We screened identified an elevated metastasis-associated SE-lncRNA SUCLG2-AS1 nasopharyngeal carcinoma (NPC) using RNA-sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) bioinformatics. Western blotting, RT-qPCR, methylated RNA immunoprecipitation (MeRIP), immunoprecipitation, chromatin pull-down 3C (chromosome conformation capture assays) were used for mechanistic studies.SUCLG2-AS1 was correlated with a poor prognosis. promotes NPC invasion metastasis while repressing apoptosis radiosensitivity vitro vivo. Mechanistically, high expression occurred m6A-dependent manner. found located region SOX2, it regulated SOX2 via long-range loop formation, which mediating CTCF (transcription factor) occupied promoter thus regulating NPC.Taken together, our data suggest that may serve novel intervention target clinical treatment NPC.

Язык: Английский

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Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk

Cell stem cell, Год журнала: 2024, Номер 31(1), С. 106 - 126.e13

Опубликована: Янв. 1, 2024

Язык: Английский

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Mesenchymal stem cells biological and biotechnological advances: Implications for clinical applications

European Journal of Pharmacology, Год журнала: 2024, Номер 977, С. 176719 - 176719

Опубликована: Июнь 6, 2024

Язык: Английский

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Mechanical forces: The missing link between idiopathic pulmonary fibrosis and lung cancer

European Journal of Cell Biology, Год журнала: 2022, Номер 101(3), С. 151234 - 151234

Опубликована: Май 10, 2022

Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of developing lung cancer compared the general population. The morbidity in IPF patient ranges from 3% to 22%, and some cases exceeds 50%, these patients reduced survival time. However, mechanisms through which increases mortality remain unclear. By carefully analyzing pathological features two diseases, we uncovered that, first, similar IPF, carcinomas are more frequently found peripheral area lungs and, second, cancers tend develop honeycomb areas IPF. In accordance above features, due spatial location, experience stretch force because average distance between adjacent alveolar cells this tends be larger than that at central when inflated; furthermore, areas, comprised condensed fibrous tissue, characterized by increased stiffness. Both coincidentally related abnormal mechanical forces (stretch tissue stiffness). Therefore, believe aberrant generated may contribute onset progression cancer. review, discuss possible effects on initiation perspective hallmarks cancer, including proliferation, metastasis, angiogenesis, stem cells, immunology, epigenetics, metabolism, so as advance our understanding pathogenesis IPF-related harness concepts for mechanotherapies.

Язык: Английский

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Mechanotransduction in Mesenchymal Stem Cells (MSCs) Differentiation: A Review

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4580 - 4580

Опубликована: Апрель 21, 2022

Mechanotransduction is the process by which physical force converted into a biochemical signal that used in development and physiology; meanwhile, it intended for ability of cells to sense respond mechanical forces activating intracellular signals transduction pathways relative phenotypic adaptation. It encompasses role stimuli developmental, morphological characteristics, biological processes different organs; response mechanically induced now also emerging as major determinant disease. Due fluid shear stress caused blood flowing tangentially across lumen surface, cardiovascular system are typically exposed variety mechanotransduction. In body, tissues continuously ranging from compression strain, pressure compressive forces. Only lately, though, has importance how shape stem cell differentiation lineage-committed can cause or exacerbate disease besides organizing been acknowledged. Mesenchymal (MSCs) potent mediators cardiac repair secret large array soluble factors have shown play huge tissue repair. Differentiation MSCs required regulate such stress, rigidity extracellular matrix through various signaling their use regenerative medicine. present review, we highlighted influences on general involved differentiation. The purpose this study demonstrate progress achieved understanding perceive react environment, well highlight areas where more research performed previous studies fill gaps.

Язык: Английский

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Peptide Hydrogels and Nanostructures Controlling Biological Machinery

Langmuir, Год журнала: 2023, Номер 39(34), С. 11935 - 11945

Опубликована: Авг. 17, 2023

Peptides are versatile building blocks for the fabrication of various nanostructures that result in formation hydrogels and nanoparticles. Precise chemical functionalization promotes discrete structure formation, causing controlled bioactivity physical properties functional materials development. The conjugation small molecules on amino acid side chains determines their intermolecular interactions addition to intrinsic peptide characteristics. Molecular information affects structure, activity. In this Perspective, blocks, nanostructure mechanisms, these discussed with results recent publications. Bioinstructive stimuli-responsive have immense impacts nanomedicine field including drug delivery, cellular engineering, regenerative medicine, biomedicine.

Язык: Английский

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Steering Stem Cell Fate within 3D Living Composite Tissues Using Stimuli‐Responsive Cell‐Adhesive Micromaterials

Advanced Science, Год журнала: 2023, Номер 10(10)

Опубликована: Янв. 4, 2023

Abstract Engineered living microtissues such as cellular spheroids and organoids have enormous potential for the study regeneration of tissues organs. Microtissues are typically engineered via self‐assembly adherent cells into spheroids, which characterized by little to no cell–material interactions. Consequently, 3D microtissue models currently lack structural biomechanical biochemical control over their internal microenvironment resulting in suboptimal functional performance limited stem cell differentiation potential. Here, this work report on stimuli‐responsive cell‐adhesive micromaterials (SCMs) that can self‐assemble with composite through integrin binding, even under serum‐free conditions. It is demonstrated SCMs homogeneously distribute within act biomechanically biochemically tunable designer materials alter tissue demand. Specifically, behavior controlled based size, stiffness, number ratio, biofunctionalization a temporal manner orthogonal secondary crosslinking strategies. Photo‐based mechanical tuning reveals early onset stiffness‐controlled lineage commitment differentiating spheroids. In contrast conventional encapsulation bulk hydrogel, incorporating cell‐sized uniquely provides cues throughout microtissues’ volume, be essential osteogenic differentiation.

Язык: Английский

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The Role of Mechanotransduction in Contact Inhibition of Locomotion and Proliferation

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2135 - 2135

Опубликована: Фев. 10, 2024

Contact inhibition (CI) represents a crucial tumor-suppressive mechanism responsible for controlling the unbridled growth of cells, thus preventing formation cancerous tissues. CI can be further categorized into two distinct yet interrelated components: locomotion (CIL) and proliferation (CIP). These components have historically been viewed as separate processes, but emerging research suggests that they may regulated by both shared pathways. Specifically, recent studies indicated CIP CIL utilize mechanotransduction pathways, process involves cells sensing responding to mechanical forces. This review article describes role in CI, shedding light on how forces regulate CIP. Emphasis is placed filamin A (FLNA)-mediated mechanotransduction, elucidating FLNA senses translates them biochemical signals cell proliferation. In addition FLNA, trans-acting factors (TAFs), which are proteins or regulatory RNAs capable directly indirectly binding specific DNA sequences distant genes gene expression, emerge sensitive players signaling pathways CI. presents methods identifying these TAF profiling associated changes chromatin structure, offering valuable insights other biological functions mediated mechanotransduction. Finally, it addresses unanswered questions fields delineates their possible future directions.

Язык: Английский

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Membrane to cortex attachment determines different mechanical phenotypes in LGR5+ and LGR5- colorectal cancer cells

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 18, 2024

Abstract Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool stem cells that express LGR5. Whether these distinct populations display different mechanical properties, how properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find compared LGR5- cells, LGR5+ stiffer, adhere better the extracellular matrix (ECM), move slower both as single clusters, higher nuclear YAP, show survival rate in response confinement, form larger transendothelial gaps. These differences largely explained by downregulation membrane cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) cells. By analyzing RNA-sequencing (scRNA-seq) expression patterns from cohort, this robust signature colorectal tumors. Our results mechanically dynamic phenotype suitable for dissemination primary tumor whereas stable resilient extravasation metastatic growth.

Язык: Английский

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Viscoelasticity in 3D Cell Culture and Regenerative Medicine: Measurement Techniques and Biological Relevance

ACS Materials Au, Год журнала: 2024, Номер 4(4), С. 354 - 384

Опубликована: Июнь 18, 2024

The field of mechanobiology is gaining prominence due to recent findings that show cells sense and respond the mechanical properties their environment through a process called mechanotransduction. cells, cell organelles, extracellular matrix are understood be viscoelastic. Various technologies have been researched developed for measuring viscoelasticity biological materials, which may provide insight into both cellular mechanisms functions Here, we explain concept introduce major techniques used measure various soft materials in different length- timescale frames. topology material undergoing testing, geometry probe, magnitude exerted stress, resulting deformation should carefully considered choose proper technique each application. Lastly, discuss several applications 3D culture tissue models regenerative medicine, including organoids, organ-on-a-chip systems, engineered constructs, tunable viscoelastic hydrogels bioprinting cell-based therapies.

Язык: Английский

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