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1.
Adv Mater ; : e2404480, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39016602

RESUMEN

Contrary to the prevailing notion that shell structures arise from the intricate chemistry and surface defects of InP quantum dots (QDs), an innovative strategy that remarkably enhances the luminescence efficiency of core-only InP QDs to over 90% is introduced. This paradigm shift is achieved through the concurrent utilization of group 2 and 3 metal-derived ligands, providing an effective remedy for surface defects and facilitating charge recombination. Specifically, a combination of Zn carboxylate and Ga chloride is employed to address the undercoordination issues associated with In and P atoms, leading to the alleviation of in-gap trap states. The intricate interplay and proportional ratio between Ga- and Zn-containing ligands play pivotal roles in attaining record-high luminescence efficiency in core-only InP QDs, as successfully demonstrated across various sizes and color emissions. Moreover, the fabrication of electroluminescent devices relying solely on InP core emission opens a new direction in optoelectronics, demonstrating the potential of the approach not only in optoelectronic applications but also in catalysis or energy conversion by charge transfer.

2.
Heliyon ; 10(10): e30518, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38770330

RESUMEN

Microplastics (MPs) and nanoplastics (NPs) are found in various environments such as aquatic, terrestrial, and aerial areas. Once ingested and inhaled, these tiny plastic debris damaged the digestive and respiratory organ systems in animals. In humans, the possible connection between MPs and various diseases such as lung diseases has been raised. Yet, the impact of MPs on the human nervous system has been unclear. Previous research using animals and cultured cells showed possible neurotoxicity of MPs and NPs. In this study, we used neural stem cells cultured from mouse subventricular zone to examine the effects of polystyrene (PS) NPs and MPs with sizes of 0.1 µm, 1 µm, and 2 µm on the cell proliferation and differentiation. We observed that only positively charged NPs and MPs, but not negatively charged ones, decreased cell viability and proliferation. These amine-modified NPs and MPs decreased both neurogenesis and oligodendrogenesis. Finally, fully differentiated neurons and oligodendrocytes were damaged and removed by the application of NPs and MPs. All these effects varied among different sizes of NPs and MPs, with the greatest effects from 1 µm and the least effects from 2 µm. These results clearly demonstrate the cytotoxicity and neurotoxicity of PS-NPs and MPs.

3.
Biomaterials ; 309: 122623, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38797121

RESUMEN

Photobiomodulation (PBM), the use of biocompatible tissue-penetrating light to interact with intracellular chromophores to modulate the fates of cells and tissues, has emerged as a promising non-invasive approach to enhancing tissue regeneration. Unlike photodynamic or photothermal therapies that require the use of photothermal agents or photosensitizers, PBM treatment does not need external agents. With its non-harmful nature, PBM has demonstrated efficacy in enhancing molecular secretions and cellular functions relevant to tissue regeneration. The utilization of low-level light from various sources in PBM targets cytochrome c oxidase, leading to increased synthesis of adenosine triphosphate, induction of growth factor secretion, activation of signaling pathways, and promotion of direct or indirect gene expression. When integrated with stem cell populations, bioactive molecules or nanoparticles, or biomaterial scaffolds, PBM proves effective in significantly improving tissue regeneration. This review consolidates findings from in vitro, in vivo, and human clinical outcomes of both PBM alone and PBM-combined therapies in tissue regeneration applications. It encompasses the background of PBM invention, optimization of PBM parameters (such as wavelength, irradiation, and exposure time), and understanding of the mechanisms for PBM to enhance tissue regeneration. The comprehensive exploration concludes with insights into future directions and perspectives for the tissue regeneration applications of PBM.


Asunto(s)
Terapia por Luz de Baja Intensidad , Regeneración , Humanos , Terapia por Luz de Baja Intensidad/métodos , Animales , Regeneración/efectos de la radiación , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Andamios del Tejido/química
4.
Adv Mater ; 36(21): e2310671, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38279779

RESUMEN

Zinc pnictides, particularly Zn3As2, hold significant promise for optoelectronic applications owing to their intrinsic p-type behavior and appropriate bandgaps. However, despite the outstanding properties of colloidal Zn3As2 nanocrystals, research in this area is lacking because of the absence of suitable precursors, occurrence of surface oxidation, and intricacy of the crystal structures. In this study, a novel and facile solution-based synthetic approach is presented for obtaining highly crystalline p-type Zn3As2 nanocrystals with accurate stoichiometry. By carefully controlling the feed ratio and reaction temperature, colloidal Zn3As2 nanocrystals are successfully obtained. Moreover, the mechanism underlying the conversion of As precursors in the initial phases of Zn3As2 synthesis is elucidated. Furthermore, these nanocrystals are employed as active layers in field-effect transistors that exhibit inherent p-type characteristics with native surface ligands. To enhance the charge transport properties, a dual passivation strategy is introduced via phase-transfer ligand exchange, leading to enhanced hole mobilities as high as 0.089 cm2 V-1 s-1. This study not only contributes to the advancement of nanocrystal synthesis, but also opens up new possibilities for previously underexplored p-type nanocrystal research.

5.
Sci Rep ; 13(1): 17325, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833341

RESUMEN

Many studies have been conducted on the transduction efficiency of recombinant adeno-associated virus (rAAV) depending on the serotype and genome structure, such as single-stranded (ss) and self-complementary (sc). To understand the variation in therapeutic efficacy, we focused on investigating subcellular distribution of viral genome depending on rAAV genome structure. It is critical to ascertain the location of the virus within the host cell after the entry because a larger amount of the viral genome placed in the nucleus facilitates viral genome replication by utilizing the host cell's system, thereby enhancing the therapeutic outcome. In this sense, tracking the location of the virus within the host cell's organelles can inform a new strategy to improve therapeutic efficacy. Therefore, we attempted to stain only the viral genome with APEX2 and DAB chemicals specifically, and the distribution of the viral genome was examined by transmission electron microscopy (TEM). Consequently, when the two types of rAAV were transduced for 6 h, scAAV2 tended to be more located in the lysosome and nucleus compared to ssAAV2.


Asunto(s)
Dependovirus , Vectores Genéticos , Transducción Genética , Dependovirus/genética , Vectores Genéticos/genética , Genoma Viral
6.
Plant Physiol ; 194(1): 491-510, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37723121

RESUMEN

Nitrogen (N) is essential for plant growth and development. Therefore, understanding its utilization is essential for improving crop productivity. However, much remains to be learned about plant N sensing and signaling. Here, rice (Oryza sativa) NUCLEAR FACTOR-YA5 (OsNF-YA5) expression was tightly regulated by N status and induced under N-deficient conditions. Overexpression (OE) of OsNF-YA5 in rice resulted in increased chlorophyll levels and delayed senescence compared to control plants under normal N conditions. Agronomic traits were significantly improved in OE plants and impaired in knockout mutants under N-deficient conditions. Using a dexamethasone-inducible system, we identified the putative targets of OsNF-YA5 that include amino acid, nitrate/peptide transporters, and NITRATE TRANSPORTER 1.1A (OsNRT1.1A), which functions as a key transporter in rice. OsNF-YA5 directly enhanced OsNRT1.1A expression and N uptake rate under N-deficient conditions. Besides, overexpression of OsNF-YA5 also enhanced the expression of GLUTAMINE SYNTHETASE 1/2 (GS1/2) and GLUTAMINE OXOGLUTARATE AMINOTRANSFERASE 1/2 (GOGAT1/2), increasing free amino acid contents under N-deficient conditions. Osa-miR169a expression showed an opposite pattern with OsNF-YA5 depending on N status. Further analysis revealed that osa-miR169a negatively regulates OsNF-YA5 expression and N utilization, demonstrating that an OsNF-YA5/osa-miR169a module tightly regulates rice N utilization for adaptation to N status.


Asunto(s)
Oryza , Proteínas de Plantas , Proteínas de Plantas/metabolismo , Oryza/metabolismo , Nitrógeno/metabolismo , Transportadores de Nitrato , Aminoácidos/metabolismo , Regulación de la Expresión Génica de las Plantas
7.
Small Methods ; 7(9): e2300206, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37160696

RESUMEN

While solution-processable colloidal quantum dots (QDs) offer cost-effective and large-scale manufacturing, they can be susceptible to subsequent solution processes, making continuous processing challenging. To enable complex and integrated device architectures, robust QD films with subsequent patterning are necessary. Here, we report a facile ligand-crosslinking strategy based on thiol-ene click chemistry. Thiol molecules added to QD films react with UV light to form radicals that crosslink with QD ligands containing carbon double bonds, enabling microscale photo-patterning of QD films and enhancing their solvent resistance. This strategy can also be extended to other ligand-capped nanocrystals. It is found that the swelling of QD films during the process of binding with the thiol molecules placed between the ligands contributes to the improvement of photoluminescence and electroluminescence properties. These results suggest that the thiol-ene crosslinking modifies the optoelectronic properties and enables direct optical patterning, expanding the potential applications of QDs.

8.
Adv Sci (Weinh) ; 10(18): e2207526, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37088787

RESUMEN

Amorphous metal oxide semiconductor phototransistors (MOTPs) integrated with colloidal quantum dots (QDs) (QD-MOTPs) are promising infrared photodetectors owing to their high photoconductive gain, low off-current level, and high compatibility with pixel circuits. However, to date, the poor mobility of conventional MOTPs, such as indium gallium zinc oxide (IGZO), and the toxicity of lead (Pb)-based QDs, such as lead sulfide and lead selenide, has limited the commercial applications of QD-MOTPs. Herein, an ultrasensitive QD-MOTP fabricated by integrating a high-mobility zinc oxynitride (ZnON)-based MOTP and lead-free indium arsenide (InAs) QDs is demonstrated. A new gradated bandgap structure is introduced in the InAs QD layer that absorbs infrared light, which prevents carriers from moving backward and effectively reduces electron-hole recombination. Chemical, optical, and structural analyses confirm the movement of the photoexcited carriers in the graded band structure. The novel QD-MOTP exhibits an outstanding performance with a responsivity of 1.15 × 105 A W-1 and detectivity of 5.32 × 1016 Jones at a light power density of 2 µW cm-2 under illumination at 905 nm.


Asunto(s)
Puntos Cuánticos , Indio , Zinc , Óxidos
9.
Sci Rep ; 12(1): 12167, 2022 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-35842484

RESUMEN

The optimized ALD infilling process for depositing Al2O3 in the vertical direction of PbS QDs enhances the photoresponsivity, relaxation rate and the air stability of PbS QDs hybrid IGZO NIR phototransistors. Infilled Al2O3, which is gradually deposited from the top of PbS QDs to the PbS/IGZO interface (1) passivates the trap sites up to the interface of PbS/IGZO without disturbing charge transfer and (2) prevents QDs deterioration caused by outside air. Therefore, an Al2O3 infilled PbS QD/IGZO hybrid phototransistor (AI-PTs) exhibited enhanced photoresponsivity from 96.4 A/W to 1.65 × 102 A/W and a relaxation time decrease from 0.52 to 0.03 s under NIR light (880 nm) compared to hybrid phototransistors without Al2O3 (RF-PTs). In addition, AI-PTs also showed improved shelf stability over 4 months compared to RF-PTs. Finally, all devices we manufactured have the potential to be manufactured in an array, and this ALD technique is a means of fabricating robust QDs/metal oxide hybrids for optoelectronic devices.

10.
Nanomaterials (Basel) ; 12(6)2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35335796

RESUMEN

Exploring bifunctional electrocatalysts to lower the activation energy barriers for sluggish electrochemical reactions for both the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are of great importance in achieving lower energy consumption and higher conversion efficiency for future energy conversion and storage system. Despite the excellent performance of precious metal-based electrocatalysts for OER and ORR, their high cost and scarcity hamper their large-scale industrial application. As alternatives to precious metal-based electrocatalysts, the development of earth-abundant and efficient catalysts with excellent electrocatalytic performance in both the OER and the ORR is urgently required. Herein, we report a core-shell CoFeS2@CoS2 heterostructure entangled with carbon nanotubes as an efficient bifunctional electrocatalyst for both the OER and the ORR. The CoFeS2@CoS2 nanocubes entangled with carbon nanotubes show superior electrochemical performance for both the OER and the ORR: a potential of 1.5 V (vs. RHE) at a current density of 10 mA cm-2 for the OER in alkaline medium and an onset potential of 0.976 V for the ORR. This work suggests a processing methodology for the development of the core-shell heterostructures with enhanced bifunctional performance for both the OER and the ORR.

11.
Nano Lett ; 21(7): 3318-3324, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33792310

RESUMEN

Strongly coupled, epitaxially fused colloidal nanocrystal (NC) solids are promising solution-processable semiconductors to realize optoelectronic devices with high carrier mobilities. Here, we demonstrate sequential, solid-state cation exchange reactions to transform epitaxially connected PbSe NC thin films into Cu2Se nanostructured thin-film intermediates and then successfully to achieve zinc-blende, CdSe NC solids with wide epitaxial necking along {100} facets. Transient photoconductivity measurements probe carrier transport at nanometer length scales and show a photoconductance of 0.28(1) cm2 V-1 s-1, the highest among CdSe NC solids reported. Atomic-layer deposition of a thin Al2O3 layer infiltrates and protects the structure from fusing into a polycrystalline thin film during annealing and further improves the photoconductance to 1.71(5) cm2 V-1 s-1 and the diffusion length to 760 nm. We fabricate field-effect transistors to study carrier transport at micron length scales and realize high electron mobilities of 35(3) cm2 V-1 s-1 with on-off ratios of 106 after doping.

12.
Nanotheranostics ; 5(1): 36-56, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391974

RESUMEN

Macrophages have been associated with drug response and resistance in diverse settings, thus raising the possibility of using macrophage imaging as a companion diagnostic to inform personalized patient treatment strategies. Nanoparticle-based contrast agents are especially promising because they efficiently deliver fluorescent, magnetic, and/or radionuclide labels by leveraging the intrinsic capacity of macrophages to accumulate nanomaterials in their role as professional phagocytes. Unfortunately, current clinical imaging modalities are limited in their ability to quantify broad molecular programs that may explain (a) which particular cell subsets a given imaging agent is actually labeling, and (b) what mechanistic role those cells play in promoting drug response or resistance. Highly multiplexed single-cell approaches including single-cell RNA sequencing (scRNAseq) have emerged as resources to help answer these questions. In this review, we query recently published scRNAseq datasets to support companion macrophage imaging, with particular focus on using dextran-based nanoparticles to predict the action of anti-cancer nanotherapies and monoclonal antibodies.


Asunto(s)
Macrófagos/citología , Humanos , Análisis de Secuencia de ARN , Análisis de la Célula Individual/métodos
13.
ACS Appl Bio Mater ; 4(7): 5678-5685, 2021 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-35006736

RESUMEN

The efficient nonviral delivery of nucleic acids into the cytoplasm is needed to fully realize the potential of gene therapy. Although cationic lipids and nanoparticles have been widely used to improve the intracellular delivery of nucleic acids, they suffer from cytotoxicity and poor endosomal escape, thus limiting the transfection efficacy. Here, we developed a photothermal transfection platform for efficient and biosafe intracellular delivery of nucleic acids. Photothermal transfection was carried out by irradiation of cells co-treated with Lipofectamine-plasmid DNA complexes and PEGylated gold nanorods (GNRs) using an NIR laser for 30 min and subsequent incubation of the cells for 30 min without laser irradiation. Compared to conventional Lipofectamine-based transfection, our photothermal transfection platform significantly improved the transfection efficiency in difficult-to-transfect human primary cells including human dermal fibroblasts while maintaining the cell viability. The photothermal heating did not leave the GNRs inside the cell, thereby minimizing the cellular damage. Furthermore, the photothermal transfection platform showed superior genome editing abilities (both gene cleavage and insertion) in human dermal fibroblasts than conventional Lipofectamine-based transfection.


Asunto(s)
Nanotubos , Ácidos Nucleicos , Edición Génica , Oro , Humanos , Transfección
14.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-33339449

RESUMEN

Drought is one of the major environmental stresses adversely affecting crop productivity worldwide. Precise characterization of genes involved in drought response is necessary to develop new crop varieties with enhanced drought tolerance. Previously, we identified 66 drought-induced miRNAs in rice plants. For the further functional investigation of the miRNAs, we applied recombinant codon-optimized Cas9 (rCas9) for rice with single-guide RNAs specifically targeting mature miRNA sequences or sites required for the biogenesis of mature miRNA. A total of 458 T0 transgenic plants were analyzed to determine the frequency and type of mutations induced by CRISPR/rCas9 on 13 independent target miRNAs. The average mutation frequency for 13 genes targeted by single guide RNAs (sgRNAs) in T0 generation was 59.4%, including mono-allelic (8.54%), bi-allelic (11.1%), and hetero-allelic combination (39.7%) mutations. The mutation frequency showed a positive correlation with Tm temperature of sgRNAs. For base insertion, one base insertion (99%) was predominantly detected in transgenic plants. Similarly, one base deletion accounted for the highest percentage, but there was also a significant percentage of cases in which more than one base was deleted. The deletion of more than two bases in OsmiR171f and OsmiR818b significantly reduced the level of corresponding mature miRNAs. Further functional analysis using CRISPR/Cas9-mediated mutagenesis confirmed that OsmiR818b is involved in drought response in rice plants. Overall, this study suggests that the CRISPR/rCas9 system is a powerful tool for loss-of-function analysis of miRNA in rice.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica/métodos , MicroARNs/genética , Oryza/genética , Fitomejoramiento/métodos , Sequías , Oryza/fisiología , Estrés Fisiológico
15.
Sensors (Basel) ; 20(18)2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32906807

RESUMEN

The analysis of circulating tumor cells (CTCs) in the peripheral blood of cancer patients is critical in clinical research for further investigation of tumor progression and metastasis. In this study, we present a novel surface-enhanced Raman scattering (SERS) substrate for the efficient capture and characterization of cancer cells using silver nanoparticles-reduced graphene oxide (AgNPs-rGO) composites. A pulsed laser reduction of silver nanowire-graphene oxide (AgNW-GO) mixture films induces hot-spot formations among AgNPs and artificial biointerfaces consisting of rGOs. We also use in situ electric field-assisted fabrication methods to enhance the roughness of the SERS substrate. The AgNW-GO mixture films, well suited for the proposed process due to its inherent electrophoretic motion, is adjusted between indium tin oxide (ITO) transparent electrodes and the nano-undulated surface is generated by applying direct-current (DC) electric fields during the laser process. As a result, MCF7 breast cancer cells are efficiently captured on the AgNPs-rGO substrates, about four times higher than the AgNWs-GO films, and the captured living cells are successfully analyzed by SERS spectroscopy. Our newly designed bifunctional substrate can be applied as an effective system for the capture and characterization of CTCs.


Asunto(s)
Nanopartículas del Metal , Células Neoplásicas Circulantes , Espectrometría Raman , Técnicas Biosensibles , Grafito , Humanos , Plata
16.
New Phytol ; 227(5): 1568-1581, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32392385

RESUMEN

Whole-genome annotation error that omits essential protein-coding genes hinders further research. We developed Target Gene Family Finder (TGFam-Finder), an alternative tool for the structural annotation of protein-coding genes containing target domain(s) of interest in plant genomes. TGFam-Finder took considerably reduced annotation run-time and improved accuracy compared to conventional annotation tools. Large-scale re-annotation of 50 plant genomes identified an average of 150, 166 and 86 additional far-red-impaired response 1, nucleotide-binding and leucine-rich-repeat, and cytochrome P450 genes, respectively, that were missed in previous annotations. We detected significantly higher number of translated genes in the new annotations using mass spectrometry data from seven plant species compared to previous annotations. TGFam-Finder along with the new gene models can provide an optimized platform for comprehensive functional, comparative, and evolutionary studies in plants.


Asunto(s)
Genoma de Planta , Plantas , Genoma de Planta/genética , Anotación de Secuencia Molecular , Plantas/genética
17.
Plant J ; 102(5): 992-1007, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31925835

RESUMEN

Sessile plants have evolved distinct mechanisms to respond and adapt to adverse environmental conditions through diverse mechanisms including RNA processing. While the role of RNA processing in the stress response is well understood for Arabidopsis thaliana, limited information is available for rice (Oryza sativa). Here, we show that OsFKBP20-1b, belonging to the immunophilin family, interacts with the splicing factor OsSR45 in both nuclear speckles and cytoplasmic foci, and plays an essential role in post-transcriptional regulation of abiotic stress response. The expression of OsFKBP20-1b was highly upregulated under various abiotic stresses. Moreover genetic analysis revealed that OsFKBP20-1b positively affected transcription and pre-mRNA splicing of stress-responsive genes under abiotic stress conditions. In osfkbp20-1b loss-of-function mutants, the expression of stress-responsive genes was downregulated, while that of their splicing variants was increased. Conversely, in plants overexpressing OsFKBP20-1b, the expression of the same stress-responsive genes was strikingly upregulated under abiotic stress. In vivo experiments demonstrated that OsFKBP20-1b directly maintains protein stability of OsSR45 splicing factor. Furthermore, we found that the plant-specific OsFKBP20-1b gene has uniquely evolved as a paralogue only in some Poaceae species. Together, our findings suggest that OsFKBP20-1b-mediated RNA processing contributes to stress adaptation in rice.


Asunto(s)
Oryza/metabolismo , Proteínas de Plantas/metabolismo , Factores de Empalme de ARN/metabolismo , Empalme Alternativo/genética , Empalme Alternativo/fisiología , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Oryza/genética , Proteínas de Plantas/genética , Unión Proteica , Procesamiento Postranscripcional del ARN/genética , Procesamiento Postranscripcional del ARN/fisiología , Factores de Empalme de ARN/genética , Estrés Fisiológico/genética , Estrés Fisiológico/fisiología
18.
J Am Chem Soc ; 141(38): 15145-15152, 2019 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-31496238

RESUMEN

The synthesis of colloidal III-V quantum dots (QDs), particularly of the arsenides and antimonides, has been limited by the lack of stable and available group V precursors. In this work, we exploit accessible InCl3- and pnictogen chloride-oleylamine as precursors to synthesize III-V QDs. Through coreduction reactions of the precursors, we achieve size- and stoichiometry-tunable binary InAs and InSb as well as ternary alloy InAs1-xSbx QDs. On the basis of structural, analytical, optical, and electrical characterization of the QDs and their thin-film assemblies, we study the effects of alloying on their particle formation and optoelectronic properties. We introduce a hydrazine-free hybrid ligand-exchange process to improve carrier transport in III-V QD thin films and realize InAs QD field-effect transistors with electron mobility > 5 cm2/(V s). We demonstrate that III-V QD thin films are promising candidate materials for infrared devices and show InAs1-xSbx QD photoconductors with superior short-wavelength infrared (SWIR) photoresponse than those of the binary QD devices.

19.
Mol Cancer Res ; 17(11): 2257-2266, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31511359

RESUMEN

ZEB1 has intrinsic oncogenic functions that control the epithelial-to-mesenchymal transition (EMT) of cancer cells, impacting tumorigenesis from its earliest stages. By integrating microenvironment signals and being implicated in feedback regulatory loops, ZEB1 appears to be a central switch that determines EMT and metastasis of cancer cells. Here, we found that ZEB1 collaborates with ELK3, a ternary complex factor belonging to the ETS family, to repress E-cadherin expression. ZEB1 functions as a transcriptional activator of ELK3. We first identified that ELK3 and ZEB1 have a positively correlated expression in breast cancer cells by using multiple databases for correlation analysis. Molecular analysis revealed that ZEB1 functions as a transcriptional activator of ELK3 expression. GST pull-down assay and coimmunoprecipitation analysis of wild-type or domain deletion mutants of ZEB1 and ELK3 showed that these 2 proteins directly bound each other. Furthermore, we demonstrated that ZEB1 and ELK3 collaborate to repress the expression of E-cadherin, a representative protein that initiates EMT. Our finding suggested that ELK3 is a novel factor of the ZEB1/E-cadherin axis in triple-negative breast cancer cells. IMPLICATIONS: ELK3 is a novel factor in the ZEB1/E-cadherin axis and ZEB1 has a dual role in ELK3 as a transcriptional activator and as a collaborator to repress E-cadherin expression in triple-negative breast cancer cells.


Asunto(s)
Cadherinas/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Proto-Oncogénicas c-ets/metabolismo , Neoplasias de la Mama Triple Negativas/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Transición Epitelial-Mesenquimal , Femenino , Humanos , Proteínas Proto-Oncogénicas c-ets/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética
20.
Sci Rep ; 9(1): 8418, 2019 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-31182803

RESUMEN

Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in the tumor microenvironment and their roles in tumor metastasis are poorly understood. Here, we report that ELK3 expressed in LECs contributes to the dissemination of cancer cells during tumor growth by providing oncogenic miRNAs to tumor cells through exosomes. We found that conditioned medium from ELK3-suppressed LECs (LCM) lost its ability to promote the migration and invasion of breast cancer cells such as MDA-MB-231, Hs578T and BT20 in vitro. Suppression of ELK3 in LECs diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo. Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro, but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. Based on the miRNA expression profiles of LECs and functional analysis, we identified miR-503-3p, miR-4269 and miR-30e-3p as downstream targets of ELK3 in LECs, which cause the above phenotype of cancer cells. These findings strongly suggest that ELK3 expressed in LECs is a major regulator that controls the communication between the tumor microenvironment and tumors to support cancer metastasis.


Asunto(s)
Neoplasias de la Mama/patología , Progresión de la Enfermedad , Células Endoteliales/metabolismo , Exosomas/metabolismo , Metástasis Linfática/patología , Vasos Linfáticos/patología , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-ets/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Células Endoteliales/efectos de los fármacos , Femenino , Humanos , Ratones Desnudos , MicroARNs/genética , Invasividad Neoplásica
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