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1.
Funct Integr Genomics ; 24(2): 37, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38374244

RESUMEN

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.


Asunto(s)
Transición Epitelial-Mesenquimal , MicroARNs , Proteína p53 Supresora de Tumor , Humanos , Línea Celular Tumoral , Proliferación Celular , Constricción Patológica , Transición Epitelial-Mesenquimal/genética , Fibroblastos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Proto-Oncogénicas c-mdm2 , Obstrucción de las Vías Aéreas/genética , Obstrucción de las Vías Aéreas/patología
2.
Phys Chem Chem Phys ; 26(5): 4683-4691, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38251932

RESUMEN

The manipulation and regulation of valley characteristics have aroused widespread interest in emerging information fields and fundamental research. Realizing valley polarization is one crucial issue for spintronic and valleytronic applications, the concepts of a half-valley metal (HVM) and ferrovalley (FV) materials have been put forward. Then, to separate electron and hole carriers, a fresh concept of a quasi-HVM (QHVM) has been proposed, in which only one type of carrier is valley polarized for electron and hole carriers. Based on first-principles calculations, we demonstrate that the Janus monolayer VSiGeP4 has QHVM character. To well regulate the QHVM state, strain engineering is utilized to adjust the electronic and valley traits of monolayer VSiGeP4. In the discussed strain range, monolayer VSiGeP4 always favors the ferromagnetic ground state and out-of-plane magnetization, which ensures the appearance of spontaneous valley polarization. It is found that the QHVM state can be induced in different electronic correlations (U), and the strain can effectively tune the valley, magnetic, and electronic features to maintain the QHVM state under various U values. Our work opens up a new research idea in the design of multifunctional spintronic and valleytronic devices.

3.
Phys Chem Chem Phys ; 25(27): 18275-18283, 2023 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-37395308

RESUMEN

Due to the presence of dissipationless edge states, the quantum anomalous Hall (QAH) insulator has garnered significant attention for both fundamental research and practical application. However, the majority of QAH insulators suffer from a low Chern number (C = 1), and the Chern number is basically unadjustable, which constrains their potential application in spintronic devices. Here, based on a tight-binding model and first-principles calculations, we propose that two-dimensional (2D) ferromagnetic monolayer NdN2 exhibits a high-Chern-number QAH effect with C = ±3, accompanied by a nontrivial band gap of 97.4 meV. More importantly, by manipulating the magnetization orientation in the xz plane, the Chern number of 2D NdN2 can be further tuned between C = ±3 and C = ±1. When the magnetization vector is confined to the xy plane, the monolayer NdN2 would exhibit either a Dirac half-semimetal or in-plane QAH phase. Moreover, the QAH effect with a higher Chern number C = 9 can be achieved by constructing a multilayer van der Waals heterostructure composed of monolayers NdN2 and BN with alternative stacking order. These findings provide a reliable platform for exploring the novel QAH effect and developing high-performance topological devices.

4.
Phys Chem Chem Phys ; 25(23): 15767-15776, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37254578

RESUMEN

Topological phase transition can be induced by electronic correlation effects combined with spin-orbit coupling (SOC). Here, based on the first-principles calculations +U approach, the influence of electronic correlation effects and SOC on topological and electronic properties of the Janus monolayer OsClBr is investigated. With intrinsic out-of-plane (OOP) magnetic anisotropy, the Janus monolayer OsClBr exhibits a sequence of states, namely, the ferrovalley (FV) to half-valley-metal (HVM) to quantum anomalous valley Hall effect (QAVHE) to HVM to FV states with increasing U values. The QAVHE is characterized by a chiral edge state linking the conduction and valence bands with a Chern number C = 1, which is closely associated with the band inversion between dx2-y2/dxy and dz2 orbitals, and sign-reversible Berry curvature. The section with larger U values (2.31-2.35 eV) is very essential for determining the new HVM and QAVHE states, and also proves that a strong electron correlation effect exists in the interior of the Janus monolayer OsClBr. When taking into consideration a representative U value (U = 2.5 eV), a valley polarization value of 157 meV can be observed, which can be switched by reversing the magnetization direction of Os atoms. It is noteworthy that the Curie temperature (TC) strongly depends on the electronic correlation effects. Our work provides a comprehensive discussion on the electronic and topological properties of the Janus monolayer OsClBr, and demonstrates that the electronic correlation effects combined with SOC can drive the emergence of QAVHE, which will open up new opportunities for valleytronic, spintronic, and topological nanoelectronic applications.

5.
Ecotoxicol Environ Saf ; 259: 115057, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37229872

RESUMEN

Metal nanoparticles (NPs) are widely used in daily life and commercial activities owing to their unique physicochemical properties. Consequently, there is an increasing risk of daily and occupational exposure to metal NPs, which raises concerns regarding their health hazards. Programmed cell deaths (PCDs) have been clarified to be involved in metal NP-induced cytotoxicity, including apoptosis, autophagy, and pyroptosis. However, whether and how ferroptosis, a newly recognized PCD, contributes to metal NP-induced cell death remain unclear. In this study, we investigated the ferroptotic effects of two representative metal NPs, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), on macrophages in vitro. Our results revealed that AgNPs, rather than AuNPs, induced non-apoptotic PCD, accompanied by lipid peroxidation and iron homeostasis disorders, which are two hallmarks of ferroptosis, in macrophages. Treatment with a ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine) reversed AgNP-induced PCD, corroborating the induction of ferroptosis upon exposure to AgNPs. Moreover, our results revealed that smaller AgNPs elicited greater ferroptotic effects on macrophages than larger ones. Importantly, ferroptosis in AgNP-treated macrophages was mainly triggered by AgNPs per se rather than by Ag ions. Overall, our study highlights the ferroptotic effects elicited by AgNPs in macrophages, which will promote the understanding of their cytotoxic effects and facilitate the safer design of metal nanoproducts.


Asunto(s)
Ferroptosis , Nanopartículas del Metal , Plata/química , Oro/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Apoptosis
6.
BMC Infect Dis ; 22(1): 181, 2022 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-35197012

RESUMEN

BACKGROUND: Chlamydia abortus is generally considered to cause abortion, stillbirth, and gestational sepsis in pregnant women, but it's rare in bloodstream infection and pneumonia. CASE PRESENTATION: We present details of a patient with bloodstream infection and pneumonia caused by Chlamydia abortus. Both blood next-generation sequencing (NGS) and sputum NGS indicate Chlamydia abortus infection. The patient received intravenous infusion of piperacillin sodium and tazobactam sodium (4.5 g/8 h) and moxifloxacin (0.4 g/d) and oral oseltamivir (75 mg/day). Within one month of follow-up, the patient's clinical symptoms were significantly improved, and all laboratory parameters showed no marked abnormality. However, chest computer tomography (CT) showed the inflammation wasn't completely absorbed. And we are still following up. CONCLUSIONS: Chlamydia abortus can cause pneumonia in humans. NGS has the particular advantage of quickly and accurately identifying the infection of such rare pathogens. Pneumonia is generally not life-threatening, and has a good prognosis with appropriate treatment. However, Chlamydia infection can lead to serious visceral complications which clinicians should pay attention to.


Asunto(s)
Infecciones por Chlamydia , Chlamydia , Neumonía , Sepsis , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Femenino , Humanos , Embarazo
7.
Bioorg Med Chem ; 58: 116645, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35151118

RESUMEN

The nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome plays an important role in microglia-mediated inflammation. Dysregulation of NLRP3 signaling results in microglial activation and triggers inflammatory responses contributing to the development of neurological disorders including ischemic stroke, schizophrenia, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Inhibition of the NLRP3-linked inflammatory pathways reduces microglia-induced inflammation and is considered as a promising therapeutic approach for neuro-inflammatory diseases. In the present study, we report the development of AMS-17, a rationally-designed tertiary sulfonylurea compound for inhibition of inflammation in microglia. AMS-17 inhibited expression of the NLRP3, and its downstream components and cytokines such as caspase-1, tumor necrosis factor-α (TNF-α), IL-1ß and inducible nitric oxide synthase (iNOS). It also suppressed lipopolysaccharide (LPS)-induced N9 microglial cell phagocytosis in vitro and activation of the microglia in mouse brain in vivo. Together, these results provide promising evidences for the inhibitory effects of AMS-17 in inflammation. This proof-of-concept study provides a new chemical scaffold, designed with the aid of pharmacophore modeling, with NLRP3 inhibitory activity which can be further developed for the treatment of inflammation-associated neurological disorders.


Asunto(s)
Inflamación/tratamiento farmacológico , Microglía/efectos de los fármacos , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Compuestos de Sulfonilurea/farmacología , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Inflamación/metabolismo , Ratones , Microglía/metabolismo , Modelos Moleculares , Estructura Molecular , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Compuestos de Sulfonilurea/síntesis química , Compuestos de Sulfonilurea/química
8.
Phys Chem Chem Phys ; 24(36): 21631-21637, 2022 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-36047444

RESUMEN

Interfaces between materials are ubiquitous in materials science, especially in devices. As device dimensions continue to be reduced, understanding the physical characteristics that appear at interfaces is crucial to exploit them for applications, spintronics in this case. Here, based on first-principles calculations, we propose a general and tunable platform to realize an exotic quantum anomalous Hall effect (QAHE) with the germanene monolayer by proximity coupling to a semiconducting ferromagnetic NiI2 (Ge/NiI2). Through analysis of the Berry curvature and band structure with spin-orbit coupling, the QAHE phase with an integer Chern number (C = -1), which is induced by band inversion between Ge-p orbitals, can achieve complete spin polarization for low-dissipation electronic devices. Also, the proximity coupling between germanene and the NiI2 substrate makes the non-trivial bandgap reach up to 85 meV, and the Curie temperature of the Ge/NiI2 heterostructure (HTS) is enhanced to 238 K, which is much higher than that of pristine NiI2. An effective k·p model is proposed to clarify the quantum phenomena in the Ge/NiI2 HTS. These findings shed light on the possible role of magnetic proximity effects on condensed matter physics in germanene and open new perspectives for multifunctional spin quantum devices in spintronics.

9.
Phys Chem Chem Phys ; 24(38): 23910-23918, 2022 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-36165573

RESUMEN

A two-dimensional (2D) multifunctional material, which couples multiple physical properties together, is both fundamentally intriguing and practically appealing. Here, based on first-principles calculations and tight-binding (TB) model analysis, the possibility of regulating the valley-contrasting physics and nontrivial topological properties via ferroelectricity is investigated in monolayer AsCH2OH. Reversible electric polarization is accessible via the rotation operation on the ligand. The broken inversion symmetry and the spin-orbit coupling (SOC) would lead to valley spin splitting, spin-valley coupling and valley-contrasting Berry curvature. More importantly, the reversal of electric polarization can realize the nonvolatile control of valley-dependent properties. Besides, the nontrivial topological state is confirmed in the monolayer AsCH2OH, which is robust against the rotation operation on the ligand. The magnitude of polarization, valley spin splitting and bulk band gap can be effectively modulated by the biaxial strain. The H-terminated SiC is demonstrated to be an appropriate candidate for encapsulating monolayer AsCH2OH, without affecting its exotic properties. These findings provide insights into the fundamental physics for the coupling of the valley-contrasting phenomenon, topological properties and ferroelectricity, and open avenues for exploiting innovative device applications.

10.
Phys Chem Chem Phys ; 24(46): 28457-28464, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36404710

RESUMEN

The exploitation of two-dimensional (2D) ferrovalley materials is of great significance in promoting the development of novel information storage devices, which is garnering increasing interest nowadays. However, the currently discovered 2D ferrovalley materials are very limited, and some of them still suffer from the drawback of small valley splitting, which seriously hinders their application in valleytronics. Herein, using first-principles calculations, we predict a promising 2D ferrovalley material, Janus monolayer GdBrI, which harbors sizable valley splitting and the anomalous valley Hall effect (AVHE). Monolayer GdBrI is a stable ferromagnetic semiconductor with an easy magnetization plane and magnetic transition temperature of 264.5 K. When the magnetization orientation is toward the z direction, valley polarization with a large splitting of 120.4 meV is achieved in the valence band due to the synergetic effect between the magnetic exchange interaction and spin-orbit coupling. The valley-contrasting Berry curvature gives rise to the AVHE in the monolayer. The magnitude of valley splitting can be continuously tuned by varying the magnetization orientation, biaxial strain and perpendicular electric field. These findings offer Janus monolayer GdBrI as a potential candidate for spintronic and valleytronic applications.

11.
Ecotoxicol Environ Saf ; 241: 113724, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35660381

RESUMEN

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with several malignancies, such as lung cancer, but little information was available about the effects of its low-dose environmental exposure in prostate cancer. Our previous study has shown that low-dose Cr(VI) exposure could promote prostate cancer(PCa) cell growth in vitro and in vivo. In the present study, we furthermore found that low-dose Cr(VI) exposure could induce DNA demethylation in PCa cells. Based on our transcriptome sequencing data and DNA methylation database, we further identified MAGEB2 as a potential effector target that contributed to tumor-promoting effect of low-dose Cr(VI) exposure in PCa. In addition, we demonstrated that MAGEB2 was upregulated in PCa and its knockdown restrained PCa cell proliferation and tumor growth in vitro and in vivo. Moreover, Co-IP and point mutation experiments confirmed that MAGEB2 could bind to the NH2-terminal NTD domain of AR through the F-box in the MAGE homology domain, and then activated AR through up-regulating its downstream targets PSA and NX3.1. Together, low-dose Cr(VI) exposure can induce DNA demethylation in prostate cancer cells, and promote cell proliferation via activating MAGEB2-AR signaling pathway. Thus, inhibition of MAGEB2-AR signaling is a novel and promising strategy to reverse low-dose Cr(VI) exposure-induced prostate tumor progression, also as effective adjuvant therapy for AR signaling-dependent PCa.


Asunto(s)
Antígenos de Neoplasias , Carcinógenos Ambientales , Proteínas de Neoplasias , Neoplasias de la Próstata , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Carcinógenos Ambientales/toxicidad , Proliferación Celular/efectos de los fármacos , Cromo/toxicidad , Humanos , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos
12.
Phys Chem Chem Phys ; 23(21): 12068-12074, 2021 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-34013305

RESUMEN

Two-dimensional (2D) Weyl semi-half-metals (WSHMs) have attracted tremendous interest for their fascinating properties combining half-metallic ferromagnetism and Weyl fermions. In this work, we present a NiCS3 monolayer as a new 2D WSHM material using systematic first-principles calculations. It has 12 fully spin-polarized Weyl nodal points in one spin channel with a Fermi velocity of 3.18 × 105 m s-1 and a fully gapped band structure in the other spin channel. It exhibits good mechanical and thermodynamic stabilities and the Curie temperature is estimated to be 403 K. The Weyl points are protected by vertical mirror plane symmetry along Γ-K, and each of them remains gapless even under spin-orbit coupling when the direction of spin is perpendicular to the Γ-K line including the Weyl point, which makes it possible to control the opening and closing of Weyl points by applying and rotating external magnetic fields. Our work not only provides a promising 2D WSHM material to explore the fundamental physics of symmetry protected ferromagnetic Weyl fermions, but also reveals a potential mechanism of band engineering of 2D WSHM materials in spintronics.

13.
Ecotoxicol Environ Saf ; 221: 112420, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34166935

RESUMEN

Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the proliferation of bladder tumor cells. Overall, our study suggested that antimony promoted bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy. These findings highlight the therapeutic potential in targeting molecules within this antimony induced-PINK1/Parkin signaling pathway and may offer a new approach for the treatment of bladder cancer.


Asunto(s)
Antimonio/toxicidad , Contaminantes Ambientales/toxicidad , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Neoplasias de la Vejiga Urinaria , Animales , Antimonio/sangre , Línea Celular Tumoral , Contaminantes Ambientales/sangre , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones Desnudos , Mitofagia/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/sangre , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
14.
Hepatology ; 70(6): 2107-2122, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31016744

RESUMEN

The growing burden of liver fibrosis and lack of effective antifibrotic therapies highlight the need for identification of pathways and complementary model systems of hepatic fibrosis. A rare, monogenic disorder in which children with mutations in mannose phosphate isomerase (MPI) develop liver fibrosis led us to explore the function of MPI and mannose metabolism in liver development and adult liver diseases. Herein, analyses of transcriptomic data from three human liver cohorts demonstrate that MPI gene expression is down-regulated proportionate to fibrosis in chronic liver diseases, including nonalcoholic fatty liver disease and hepatitis B virus. Depletion of MPI in zebrafish liver in vivo and in human hepatic stellate cell (HSC) lines in culture activates fibrotic responses, indicating that loss of MPI promotes HSC activation. We further demonstrate that mannose supplementation can attenuate HSC activation, leading to reduced fibrogenic activation in zebrafish, culture-activated HSCs, and in ethanol-activated HSCs. Conclusion: These data indicate the prospect that modulation of mannose metabolism pathways could reduce HSC activation and improve hepatic fibrosis.


Asunto(s)
Células Estrelladas Hepáticas/fisiología , Cirrosis Hepática/etiología , Manosa-6-Fosfato Isomerasa/fisiología , Manosa/farmacología , Animales , Células Cultivadas , Glicosilación , Humanos , Masculino , Factor de Crecimiento Derivado de Plaquetas/fisiología , Transducción de Señal/fisiología , Pez Cebra
15.
Phys Chem Chem Phys ; 22(46): 27024-27030, 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33210701

RESUMEN

Nodal-line half-metals (NLHMs) are highly desirable for future spintronic devices due to their exotic quantum properties. However, the experimental realization in spin-polarized materials is nontrivial to date. Herein we perform first-principles calculations to demonstrate a 2D honeycomb, AgN, as a promising candidate of NLHMs, which is thermodynamically and dynamically stable. Band structure analysis reveals that two concentric NLs coexist centered at a Γ point near EF, accompanied by the electron and hole pockets that touch each other linearly with single-spin components. Inclusion of SOC can enrich the electronic structures of AgN, sensitive to the protection of mirror reflection symmetry: the NLHM survives if the spin is perpendicular to the Mz mirror plane, while it tunes into Wyle nodal-points by rotating spins from the out-of-plane to the in-plane direction. The characteristics of HM and NL can be well maintained on semiconducting h-BN and is immune to mechanical strains. These tunable magnetic properties render 2D AgN suitable for exotic quantum transports in nodal fermions as well as related spintronic devices.

16.
Phys Chem Chem Phys ; 22(9): 5163-5169, 2020 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-32083263

RESUMEN

Opening up a band gap without lowering high carrier mobility in germanene and finding suitable substrate materials to form van der Waals heterostructures have recently emerged as an intriguing way of designing a new type of electronic devices. By using first-principles calculations, here, we systematically investigate the effect of the GaGeTe substrate on the electronic properties of monolayer germanene. Linear dichroism of the Dirac-cone like band dispersion and higher carrier mobility (9.7 × 103 cm2 V-1 s-1) in the Ge/GaGeTe heterostructure (HTS) are found to be preserved compared to that of free-standing germanene. Remarkably, the band structure of HTS can be flexibly modulated by applying bias voltage or strain. A prototype data storage device FET based on Ge/GaGeTe HTS is proposed, which presents a promising high performance platform with a tunable band gap and high carrier mobility.

17.
Carcinogenesis ; 40(1): 52-60, 2019 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-30247545

RESUMEN

Ribosomal stress is known to increase cancer risk; however, the molecular mechanism underlying its various effects on cancer remains unclear. To decipher this puzzle, we investigated the upstream signaling pathway that might be involved in promoting ribosomal stress that leads to tumor progression. Our results suggested that inhibition of kinase PIM1 attenuated PC3 cell growth and motility following the condensed cellular body and decreased protein translation in PIM1-inhibited cells. In addition, PIM1 was found to be a component of the small 40S ribosomal subunit and could regulate the expression of ribosomal small subunit protein 7 (RPS7). Our investigation also revealed that PIM1 enhanced the protein stability of c-Myc. Furthermore, a functional E-box motif was found upstream of the transcription start site in RPS7, and RPS7 has been proven to be a transcriptional target of c-Myc. Additionally, knocking down RPS7 dramatically reduced cell growth in vitro and in vivo, whereas enhancing RPS7 expression reversed the condensed cellular body and decreased protein translation resulted from PIM1 inhibition. Finally, biochemical recurrence-free survival and overall survival analysis indicated that the concomitant upregulation of PIM1 and RPS7 correlated with the worst prognosis of prostate cancer (PCa). Overall, our results demonstrated that kinase PIM1 promotes cell growth through c-Myc-RPS7-induced ribosomal stress in PCa. These findings substantially expanded our understanding on the molecular mechanism of PIM1-promoted abnormal ribosomal biosynthesis in tumorigenesis and tumor progression in PCa. Therapies that target molecules involved in PIM1-RPS7-induced ribosomal stress could provide a promising approach to treating PCa.


Asunto(s)
Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-myc/fisiología , Proteínas Proto-Oncogénicas c-pim-1/fisiología , Proteínas Ribosómicas/fisiología , Ribosomas/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-pim-1/antagonistas & inhibidores , Subunidades Ribosómicas Pequeñas de Eucariotas/fisiología
18.
Prostate ; 79(11): 1199-1210, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31251827

RESUMEN

BACKGROUND: With the popularity of serum prostate-specific antigen (PSA) screening, the number of newly diagnosed prostate cancer (PCa) patients is increasing. However, indolent or invasive PCa cannot be distinguished by PSA levels. Here, we mainly explored the role of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the invasiveness of PCa. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis was used to detect the expressions of hnRNPM in PCa and benign prostate hyperplasia (BPH) tissues as well as in PCa cell lines. Immunohistochemistry was applied to detect the hnRNPM or Yin Yang 1 (YY1) expression in BPH, prostate adenocarcinoma (ADENO) and neuroendocrine prostate cancer (NEPC) tissues. After aberrant, the expression of hnRNPM in C4-2 and PC3 cells, the changes of cell migration and invasion were observed through wound-healing and transwell assays. We also predicted the transcription factor of hnRNPM through databases, then verified the association of hnRNPM and YY1 using chromatin immunoprecipitation (ChIP) and luciferase assays. RESULTS: The expression level of hnRNPM is gradually reduced in BPH, ADENO, and NEPC tissues and it is less expressed in more aggressive PCa cell lines. Overexpression of hnRNPM can significantly reduce Twist1 expression, which inhibits the migration and invasion of PCa cells in vitro. In PCa cells, overexpression of YY1 can promote epithelial-mesenchymal transition by reducing hnRNPM expression. Furthermore, this effect caused by overexpression of YY1 can be partially attenuated by simultaneous overexpression of hnRNPM. CONCLUSIONS: Our study demonstrates that hnRNPM negatively regulated PCa cell migration and invasion, and its expression can be transcriptionally inhibited by YY1. We speculated that hnRNPM may be a biomarker to assist in judging the aggressiveness of PCa.


Asunto(s)
Adenocarcinoma/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Ribonucleoproteína Heterogénea-Nuclear Grupo M/metabolismo , Invasividad Neoplásica/genética , Neoplasias de la Próstata/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patología , Línea Celular Tumoral , Movimiento Celular/fisiología , Regulación Neoplásica de la Expresión Génica , Ribonucleoproteína Heterogénea-Nuclear Grupo M/genética , Humanos , Masculino , Invasividad Neoplásica/patología , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismo
19.
Anticancer Drugs ; 30(7): e0773, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30807553

RESUMEN

Proteasome α5 subunit (PSMA5) is related to poor prognosis in various cancers. The first therapeutic proteasome inhibitor, bortezomib, induces apoptosis, suppressing cell growth in many tumor types. However, the effects of PSMA5 and bortezomib in prostate cancer (PCa) are still unknown. In this study, we investigated whether PSMA5 is associated with the tumorigenic progression and the interaction of PSMA5 with bortezomib in PCa. We knocked down PSMA5 with siRNA and studied the changes in cell viability and motility with Cell Counting Kit-8, quantitative PCR, fluorescence-activated cell sorting, scratch, and invasion assays. We also investigated the effect of PSMA5 in PCa cells treated with bortezomib and in those that are resistant to bortezomib. We found that silencing PSMA5 inhibited cell proliferation, induced apoptosis, restricted cell migration and invasion, and demonstrated a coordinated effect with bortezomib. Cells resistant to bortezomib gained sensitivity to bortezomib after PSMA5 was knocked down. Our results show, for the first time, that PSMA5 promotes the tumorigenic process of PCa and is linked to bortezomib resistance.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Bortezomib/farmacología , Carcinogénesis/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de la Próstata/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Carcinogénesis/efectos de los fármacos , Carcinogénesis/metabolismo , Movimiento Celular , Proliferación Celular , Humanos , Masculino , Invasividad Neoplásica , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Células Tumorales Cultivadas
20.
Phys Chem Chem Phys ; 21(9): 5165-5169, 2019 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-30775766

RESUMEN

Ferroelasticity and band topology are two intriguing yet distinct quantum states of condensed matter materials. Their coexistence in a single two-dimensional (2D) lattice, however, has never been observed. Here, we found that the 2D tetragonal HfC monolayer allowed simultaneous presence of ferroelastic and topological orders. By using first-principles calculations, we found that it could allow a low switching barrier with reversible strain of 17.4%, indicating that the anisotropic properties are achievable experimentally for a 2D tetragonal lattice. More interestingly, the tuning of topological behaviors with strain led to spin-separated and gapless edge states, that is, the quantum spin Hall effect. These findings from the coupling of two quantum orders offer insights into ferroelastic control over topological edge states for achieving multifunctional properties in next-generation 2D nanodevices.

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