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1.
Nature ; 627(8002): 67-72, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38448698

RESUMEN

Ordinary metals contain electron liquids within well-defined 'Fermi' surfaces at which the electrons behave as if they were non-interacting. In the absence of transitions to entirely new phases such as insulators or superconductors, interactions between electrons induce scattering that is quadratic in the deviation of the binding energy from the Fermi level. A long-standing puzzle is that certain materials do not fit this 'Fermi liquid' description. A common feature is strong interactions between electrons relative to their kinetic energies. One route to this regime is special lattices to reduce the electron kinetic energies. Twisted bilayer graphene1-4 is an example, and trihexagonal tiling lattices (triangular 'kagome'), with all corner sites removed on a 2 × 2 superlattice, can also host narrow electron bands5 for which interaction effects would be enhanced. Here we describe spectroscopy revealing non-Fermi-liquid behaviour for the ferromagnetic kagome metal Fe3Sn2 (ref. 6). We discover three C3-symmetric electron pockets at the Brillouin zone centre, two of which are expected from density functional theory. The third and most sharply defined band emerges at low temperatures and binding energies by means of fractionalization of one of the other two, most likely on the account of enhanced electron-electron interactions owing to a flat band predicted to lie just above the Fermi level. Our discovery opens the topic of how such many-body physics involving flat bands7,8 could differ depending on whether they arise from lattice geometry or from strongly localized atomic orbitals9,10.

2.
J Immunol ; 210(8): 1074-1085, 2023 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-36897229

RESUMEN

Influenza A viruses (IAVs) and influenza B viruses (IBVs) cause annual epidemics in human populations with seasonal circulation spikes. Peptide AM58-66GL9 located at residues 58-66 of M1 protein of IAVs has been recognized as an immunodominant T cell epitope with HLA-A*0201 restriction and broadly used as a positive reference in influenza immunity. This peptide also almost completely overlaps with a nuclear export signal (NES) 59-68 in IAV M1, which explains the limited escape mutations under the T cell immune pressure in this region. In this study, we investigated the potential immunogenicity and NES in the corresponding region of IBV. The long peptide covering this region can be recognized by specific T cells and induce robust expression of IFN-γ among HLA-B*1501 donors in vivo, but not in HLA-A*0201 donors. Among a series of truncated peptides derived from this region, we identified an immunodominant HLA-B*1501-restricted T cell epitope BM58-66AF9 (ALIGASICF) in the M1 protein of IBV. Furthermore, the structure of the HLA-B*1501/BM58-66AF9 complex shows that BM58-66AF9 performs a flat and featureless conformation that is similar to AM58-66GL9 presented by HLA-A*0201. In contrast with IAV, the sequence around residues 55-70 of IBV M1 does not contain an NES. Our comparative study on IBVs and IAVs provides new insights into the immune and evolution characteristics of IBVs and may shed light on vaccine development for influenza viruses.


Asunto(s)
Virus de la Influenza A , Gripe Humana , Humanos , Animales , Señales de Exportación Nuclear , Epítopos de Linfocito T , Virus de la Influenza B , Antígenos HLA-B/genética , Estadios del Ciclo de Vida
3.
Nature ; 567(7749): 496-499, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30894751

RESUMEN

Chirality-the geometric property of objects that do not coincide with their mirror image-is found in nature, for example, in molecules, crystals, galaxies and life forms. In quantum field theory, the chirality of a massless particle is defined by whether the directions of its spin and motion are parallel or antiparallel. Although massless chiral fermions-Weyl fermions-were predicted 90 years ago, their existence as fundamental particles has not been experimentally confirmed. However, their analogues have been observed as quasiparticles in condensed matter systems. In addition to Weyl fermions1-4, theorists have proposed a number of unconventional (that is, beyond the standard model) chiral fermions in condensed matter systems5-8, but direct experimental evidence of their existence is still lacking. Here, by using angle-resolved photoemission spectroscopy, we reveal two types of unconventional chiral fermion-spin-1 and charge-2 fermions-at the band-crossing points near the Fermi level in CoSi. The projections of these chiral fermions on the (001) surface are connected by giant Fermi arcs traversing the entire surface Brillouin zone. These chiral fermions are enforced at the centre or corner of the bulk Brillouin zone by the crystal symmetries, making CoSi a system with only one pair of chiral nodes with large separation in momentum space and extremely long surface Fermi arcs, in sharp contrast to Weyl semimetals, which have multiple pairs of Weyl nodes with small separation. Our results confirm the existence of unconventional chiral fermions and provide a platform for exploring the physical properties associated with chiral fermions.

4.
Mol Ther ; 32(5): 1510-1525, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38454605

RESUMEN

The acute respiratory virus infection can induce uncontrolled inflammatory responses, such as cytokine storm and viral pneumonia, which are the major causes of death in clinical cases. Cyclophilin A (CypA) is mainly distributed in the cytoplasm of resting cells and released into the extracellular space in response to inflammatory stimuli. Extracellular CypA (eCypA) is upregulated and promotes inflammatory response in severe COVID-19 patients. However, how eCypA promotes virus-induced inflammatory response remains elusive. Here, we observe that eCypA is induced by influenza A and B viruses and SARS-CoV-2 in cells, mice, or patients. Anti-CypA mAb reduces pro-inflammatory cytokines production, leukocytes infiltration, and lung injury in virus-infected mice. Mechanistically, eCypA binding to integrin ß2 triggers integrin activation, thereby facilitating leukocyte trafficking and cytokines production via the focal adhesion kinase (FAK)/GTPase and FAK/ERK/P65 pathways, respectively. These functions are suppressed by the anti-CypA mAb that specifically blocks eCypA-integrin ß2 interaction. Overall, our findings reveal that eCypA-integrin ß2 signaling mediates virus-induced inflammatory response, indicating that eCypA is a potential target for antibody therapy against viral pneumonia.


Asunto(s)
COVID-19 , Ciclofilina A , Ciclofilina A/metabolismo , Animales , Humanos , Ratones , COVID-19/metabolismo , COVID-19/virología , COVID-19/inmunología , Antígenos CD18/metabolismo , SARS-CoV-2 , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Neumonía Viral/metabolismo , Neumonía Viral/inmunología , Citocinas/metabolismo , Anticuerpos Monoclonales/farmacología , Transducción de Señal , Virus de la Influenza A , Modelos Animales de Enfermedad
5.
Liver Int ; 44(7): 1634-1650, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38517158

RESUMEN

BACKGROUND: Excessive fatty acids in the liver lead to the accumulation of lipotoxic lipids and then cellular stress to further evoke the related disease, like non-alcoholic fatty liver disease (NAFLD). As reported, fatty acid stimulation can cause some specific miRNA dysregulation, which caused us to investigate the relationship between miRNA biogenesis and fatty acid overload. METHODS: Gene expression omnibus (GEO) dataset analysis, miRNA-seq, miRNA cleavage assay, RT-qPCR, western blotting, immunofluorescence and co-immunoprecipitation (co-IP) were used to reveal the change of miRNAs under pathological status and explore the relevant mechanism. High fat, high fructose, high cholesterol (HFHFrHC) diet-fed mice transfected with AAV2/8-shDrosha or AAV2/8-shPRMT5 were established to investigate the in vivo effects of Drosha or PRMT5 on NAFLD phenotype. RESULTS: We discovered that the cleavage of miRNAs was inhibited by analysing miRNA contents and detecting some representative pri-miRNAs in multiple mouse and cell models, which was further verified by the reduction of the Microprocessor activity in the presence of palmitic acid (PA). In vitro, PA could induce Drosha, the core RNase III in the Microprocessor complex, degrading through the proteasome-mediated pathway, while in vivo, knockdown of Drosha significantly promoted NAFLD to develop to a more serious stage. Mechanistically, our results demonstrated that PA can increase the methyltransferase activity of PRMT5 to degrade Drosha through MDM2, a ubiquitin E3 ligase for Drosha. The above results indicated that PRMT5 may be a critical regulator in lipid metabolism during NAFLD, which was confirmed by the knocking down of PRMT5 improved aberrant lipid metabolism in vitro and in vivo. CONCLUSIONS: We first demonstrated the relationship between miRNA dosage and NAFLD and proved that PA can activate the PRMT5-MDM2-Drosha signalling pathway to regulate miRNA biogenesis.


Asunto(s)
Metabolismo de los Lípidos , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Proteína-Arginina N-Metiltransferasas , Proteínas Proto-Oncogénicas c-mdm2 , Animales , Humanos , Masculino , Ratones , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Ácidos Grasos/metabolismo , Hígado/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , MicroARNs/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Ribonucleasa III/metabolismo , Ribonucleasa III/genética , Transducción de Señal
6.
Pharmacol Res ; 203: 107159, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554790

RESUMEN

Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science).


Asunto(s)
Citocinas , Oftalmopatías , Humanos , Citocinas/metabolismo , Animales , Oftalmopatías/terapia , Oftalmopatías/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Encapsulación Celular/métodos
7.
Nat Mater ; 21(4): 423-429, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35190656

RESUMEN

Charge neutrality and their expected itinerant nature makes excitons potential transmitters of information. However, exciton mobility remains inaccessible to traditional optical experiments that only create and detect excitons with negligible momentum. Here, using angle-resolved photoemission spectroscopy, we detect dispersing excitons in the quasi-one-dimensional metallic trichalcogenide, TaSe3. The low density of conduction electrons and the low dimensionality in TaSe3 combined with a polaronic renormalization of the conduction band and the poorly screened interaction between these polarons and photo-induced valence holes leads to various excitonic bound states that we interpret as intrachain and interchain excitons, and possibly trions. The thresholds for the formation of a photo-hole together with an exciton appear as side valence bands with dispersions nearly parallel to the main valence band, but shifted to lower excitation energies. The energy separation between side and main valence bands can be controlled by surface doping, enabling the tuning of certain exciton properties.


Asunto(s)
Electrones
8.
Opt Express ; 31(14): 23589-23597, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37475439

RESUMEN

"Naked" ferroferric-oxide nanoparticles (FONPs) synthesized by a femtosecond laser ablation on a bulk stainless steel in liquid were applied to the Nd: YVO4 laser to achieve passive Q-switched pulse laser output. Without the pollution of ligand, the inherent light characteristic of "naked" FONPs was unaffected. The analysis of the morphological characteristics, dominant chemical elements, and phase composition of the FONPs showed that they were mainly composed of Fe3O4, which was spherical with an average diameter of 40 nm. The electron transition and orbital splitting of the iron element's octahedral center position under the laser-driven were considered the primary mechanisms of saturable absorption of Fe3O4 nanoparticles.

9.
Opt Express ; 31(14): 22372-22384, 2023 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-37475349

RESUMEN

Based on Dammann vortex grating and adaptive gain stochastic parallel gradient descent algorithm, we theoretically proposed a phase control technology scheme of the coherent beam combining system for generating perfect vectorial vortex beams (VVBs). The simulated results demonstrate that the discrete phase locking for different types of VVBs (including vortex beams, vector beams, and generalized VVBs) can be successfully realized. The intensity distributions, polarization orientation, Pancharatnam phases, and beam widths of different |Hm,n〉 states with the obtained discrete phase distribution further prove that the generated beams are perfect VVBs. Subsequently, the phase aberration residual for different VVBs is evaluated using the normalized phase cosine distance function, and their values range from 0.01 to 0.08, which indicates the obtained discrete phase distribution is close to the ideal phase distribution. In addition, benefitting from the high bandwidth of involved devices in the proposed scheme, the influence of dynamic phase noise can be negligible. The proposed method could be beneficial to realize and switch flexible perfect VVBs in further applications.

10.
Opt Express ; 31(7): 11885-11898, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-37155813

RESUMEN

Based on coherent beam combining, we propose a method for generating the perfect vectorial vortex beams (VVBs) with a specially designed radial phase-locked Gaussian laser array, which is composed of two discrete vortex arrays with right-handed (RH) and left-handed (LH) circularly polarized states and in turn adjacent to each other. The simulation results demonstrate that the VVBs with correct polarization order and topological Pancharatnam charge are successfully generated. The diameter and thickness of generated VVBs independent of the polarization orders and topological Pancharatnam charges further prove that the generated VVBs are perfect. Propagating in free space, the generated perfect VVBs can be stable for a certain distance, even with half-integer orbital angular momentum. In addition, constant phases φ0 between the RH and LH circularly polarized laser arrays has no effect on polarization order and topological Pancharatnam charge but makes polarization orientation to rotate φ0/2. Moreover, perfect VVBs with elliptically polarized states can be flexibly generated only by adjusting the intensity ratio between the RH and LH circularly polarized laser array, and such perfect VVBs are also stable on beam propagation. The proposed method could provide a valuable guidance for high power perfect VVBs in future applications.

11.
Fish Shellfish Immunol ; 139: 108852, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37295735

RESUMEN

Cathepsins belong to a group of proteins that are present in both prokaryotic and eukaryotic organisms and have an extremely high degree of evolutionary conservation. These proteins are functionally active in extracellular environments as soluble enzymatic proteins or attached to plasma membrane receptors. In addition, they occur in cellular secretory vesicles, mitochondria, the cytosol, and within the nuclei of eukaryotic cells. Cathepsins are classified into various groups based on their sequence variations, leading to their structural and functional diversification. The molecular understanding of the physiology of crustaceans has shown that proteases, including cathepsins, are expressed ubiquitously. They also contain one of the central regulatory systems for crustacean reproduction, growth, and immune responses. This review focuses on various aspects of the crustaceans cathepsins and emphasizes their biological roles in different physiological processes such as reproduction, growth, development, and immune responses. We also describe the bioactivity of crustaceans cathepsins. Because of the vital biological roles that cathepsins play as cellular proteases in physiological processes, they have been proposed as potential novel targets for the development of management strategies for the aquaculture industries.


Asunto(s)
Catepsinas , Fenómenos Fisiológicos , Animales , Catepsinas/genética , Catepsinas/química , Proteínas , Evolución Biológica
12.
Opt Express ; 30(4): 4905-4918, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35209463

RESUMEN

The segmented planar imager is an advanced optical interferometric telescope with a photonic integrated circuit (PIC). It provides a significant reduction in size, weight, and power consumption as compared to traditional optical interferometry. In this article, we propose the combination of a single PIC with a two-dimensional (2D) lens array to achieve single-PIC imaging. Unlike previous designs which require a large number of PIC arrangements in different directions for imaging, a single-PIC imaging system requires only one PIC for 2D frequency domain sampling and imaging. In addition, the single-PIC imaging system can form a larger equivalent aperture through modularization. Since PIC can be mass-produced, the modularization ability of the single-PIC imaging system greatly shortens the production and development cycle of large-aperture telescopes.

13.
Opt Lett ; 47(18): 4596-4599, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36107041

RESUMEN

Compared with the traditional imaging systems, segmented planar imaging technology has the advantages of low mess, small size, and low power in the same resolution situation. To obtain relatively complete frequency domain coverage, the lenslet array requires a large number of lenslets, and the photonic integrated circuit board requires a large number of optical devices, which limits the application and development of the segmented planar imaging technology. In this paper, we introduce a novel, to the best of our knowledge, design of the photonic integrated circuit to ensure that each lenslet in the lenslet array can form a baseline with any other lenslets. This breaks the barrier between segmented planar imaging technology and the traditional synthetic aperture, giving segmented planar imaging technology a sufficient number of frequency domain samples and a concise photonic integrated circuit structure.

14.
FASEB J ; 35(11): e21958, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34606626

RESUMEN

Cyclophilin A (CypA), a member of the cyclophilin family, plays a vital role in microorganismal infections, inflammatory diseases, and cancers. Interleukin-6 (IL-6) is a pleiotropic cytokine, exerting variety of effects on inflammation, immune response, hematopoiesis, and tumor proliferation. Binding of IL-6 to soluble IL-6 receptor (sIL-6R) induces pro-inflammatory trans-signaling, which has been described to be stronger than anti-inflammatory classic signaling triggered by the binding of IL-6 to membrane-bound IL-6 receptor. Here we found that upon the treatment of IL-6 and sIL-6R, CypA inhibited the ubiquitination-mediated degradation of IL-6 membrane receptor gp130 and enhanced its dimerization, thereby positively regulated the IL-6 trans-signaling and increased the expression of downstream iNOS, IL-6, and CypA. Furthermore, CypA expression could be negatively regulated by suppressor of cytokine signaling 1 (SOCS1). The SH2 and Box domains of SOCS1 interacted with CypA and promoted its K48-linked ubiquitination-mediated degradation, which inhibited the IL-6 trans-signaling pathway. Collectively, our findings reveal an important role of CypA in the positive and negative feedback regulation of the IL-6 trans-signaling pathway.


Asunto(s)
Ciclofilina A/fisiología , Interleucina-6/metabolismo , Receptores de Interleucina-6/metabolismo , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Células A549 , Células HEK293 , Humanos , Transducción de Señal
15.
Appl Opt ; 61(17): 5010, 2022 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-36256177

RESUMEN

This erratum reports corrections in Figs. 5 and 8 of our previous paper [Appl. Opt.60, 7921 (2021)APOPAI0003-693510.1364/AO.431678].


Asunto(s)
Radiación Terahertz , Técnicas Biosensibles
16.
Entropy (Basel) ; 24(4)2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35455134

RESUMEN

With the development and appliance of multi-agent systems, multi-agent cooperation is becoming an important problem in artificial intelligence. Multi-agent reinforcement learning (MARL) is one of the most effective methods for solving multi-agent cooperative tasks. However, the huge sample complexity of traditional reinforcement learning methods results in two kinds of training waste in MARL for cooperative tasks: all homogeneous agents are trained independently and repetitively, and multi-agent systems need training from scratch when adding a new teammate. To tackle these two problems, we propose the knowledge reuse methods of MARL. On the one hand, this paper proposes sharing experience and policy within agents to mitigate training waste. On the other hand, this paper proposes reusing the policies learned by original teams to avoid knowledge waste when adding a new agent. Experimentally, the Pursuit task demonstrates how sharing experience and policy can accelerate the training speed and enhance the performance simultaneously. Additionally, transferring the learned policies from the N-agent enables the (N+1)-agent team to immediately perform cooperative tasks successfully, and only a minor training resource can allow the multi-agents to reach optimal performance identical to that from scratch.

17.
Entropy (Basel) ; 24(6)2022 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-35741495

RESUMEN

Poker has been considered a challenging problem in both artificial intelligence and game theory because poker is characterized by imperfect information and uncertainty, which are similar to many realistic problems like auctioning, pricing, cyber security, and operations. However, it is not clear that playing an equilibrium policy in multi-player games would be wise so far, and it is infeasible to theoretically validate whether a policy is optimal. Therefore, designing an effective optimal policy learning method has more realistic significance. This paper proposes an optimal policy learning method for multi-player poker games based on Actor-Critic reinforcement learning. Firstly, this paper builds the Actor network to make decisions with imperfect information and the Critic network to evaluate policies with perfect information. Secondly, this paper proposes a novel multi-player poker policy update method: asynchronous policy update algorithm (APU) and dual-network asynchronous policy update algorithm (Dual-APU) for multi-player multi-policy scenarios and multi-player sharing-policy scenarios, respectively. Finally, this paper takes the most popular six-player Texas hold 'em poker to validate the performance of the proposed optimal policy learning method. The experiments demonstrate the policies learned by the proposed methods perform well and gain steadily compared with the existing approaches. In sum, the policy learning methods of imperfect information games based on Actor-Critic reinforcement learning perform well on poker and can be transferred to other imperfect information games. Such training with perfect information and testing with imperfect information models show an effective and explainable approach to learning an approximately optimal policy.

18.
Opt Express ; 29(12): 18010-18025, 2021 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-34154070

RESUMEN

A cycloid-like variable curvature mirror (VCM) for zoom-imaging systems was investigated. An analytical-deformation solution to a thin-elastic plate with a cycloid-like thickness distribution and simply supported boundary condition under uniform pressure was found using a small parameter method. The finite-element analysis of the thin-elastic plate and designed VCM showed a good correlation with the analytical solution. The VCM was manufactured and polished to the initial shape with a root mean square (RMS) of 1/80λ. Finally, with air-pressure-based actuation testing under 0.07 MPa, the VCM deforms approximately 36.89 µm and maintains the RMS surface performance of 1/10λ, 1/40λ with and without spherical aberrations, respectively.

19.
Appl Opt ; 60(26): 7921-7928, 2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34613051

RESUMEN

By taking advantage of dielectric metasurfaces and plasmonic nanostructures, a terahertz photoconductive antenna (THz-PCA) is proposed and investigated in detail. The designed dielectric metasurfaces can reduce the optical reflection down to 1.4% and accelerate the switching process (electric conductive to resistive) that broadens the THz spectrum emitted from THz-PCA. Simultaneously, the embedded plasmonic nanostructures can realize 11.2 times enhancement in local electric field without affecting the switching process and the damage threshold of the THz-PCA. Simulated results indicate that the proposed THz-PCA is 70.56 times stronger in THz radiation power than that of the traditional THz-PCA. The significant enhancement ensures the proposed THz-PCA has great prospects in promoting THz technology based on the THz-PCA.

20.
Acta Biochim Biophys Sin (Shanghai) ; 53(9): 1198-1206, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34327529

RESUMEN

Breast cancer is the most prevalent malignancy among women worldwide. Paclitaxel (Taxol) is a widely applied chemotherapeutic agent against breast cancer. Although Taxol therapy has achieved improvements recently, development of chemoresistance of breast cancer patients is a major obstacle, leading to therapeutic failure. Long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis and progresses of breast cancer. However, the biological roles and molecular targets of lncRNA NEAT1 in Taxol-resistant breast cancer remain unclear. Here, we report that NEAT1 is significantly upregulated in breast tumors and cell lines. In addition, silencing NEAT1 effectively sensitizes breast cancer cells to Taxol. Bioinformatical analysis and luciferase assay demonstrated that miR-23a-3p could be sponged and downregulated by NEAT1. We demonstrated that miR-23a-3p was downregulated and functioned as a tumor suppressor in breast cancer. Furthermore, in the established Taxol-resistant MDA-MB-231 breast cancer cell line, we detected significantly increased NEAT1 expression and downregulated miR-23a-3p expression. Importantly, FOXA1 was identified and validated as a direct target of miR-23a-3p in breast cancer cells. Rescue experiments demonstrated that the restoration of miR-23a-3p in NEAT1-overexpressing Taxol-resistant breast cancer cells successfully overcame the NEAT1-promoted Taxol resistance. Taken together, our results revealed the clinical roles and molecular mechanisms for the NEAT1-mediated chemoresistance, providing new insights into the development of non-coding RNA-based therapeutic strategies for enhancing the anti-cancer effects of traditional chemotherapeutic drugs.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Resistencia a Antineoplásicos , Factor Nuclear 3-alfa del Hepatocito/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Adulto , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Supresores de Tumor , Factor Nuclear 3-alfa del Hepatocito/genética , Humanos , MicroARNs/genética , Persona de Mediana Edad , Paclitaxel/farmacología , ARN Largo no Codificante/genética , Regulación hacia Arriba/genética , Adulto Joven
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