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1.
J Cell Mol Med ; 27(22): 3526-3538, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37698037

RESUMO

Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Células-Tronco Mesenquimais , MicroRNAs , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Exossomos/metabolismo , Camundongos Nus , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Carcinogênese/patologia
2.
Natl Sci Rev ; 10(1): nwac058, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36789105

RESUMO

Photoacoustic imaging, an acoustic imaging modality with potentially optical resolution in an optical turbid medium, has attracted great attention. However, the convergence of wavefront optimization and raster scanning in computational photoacoustic imaging leads to the challenge of fast mapping, especially for a spatial resolution approaching the acoustic deep-subwavelength regime. As a sparse sampling paradigm, compressive sensing has been applied in numerous fields to accelerate data acquisition without significant quality losses. In this work, we propose a dual-compressed approach for photoacoustic surface tomography that enables high-efficiency imaging with 3D spatial resolution unlimited by the acoustics in a turbid environment. The dual-compressed photoacoustic imaging with single-pixel detection, enabled by spatially optical modulation with synchronized temporally photoacoustic coding, allows decoding of the fine optical information from the modulated acoustic signal even when the variance of original photoacoustic signals is weak. We perform a proof-of-principle numerical demonstration of dual-compressed photoacoustic imaging, that resolves acoustic sub-acoustic-wavelength details with a significantly reduced number of measurements, revealing the potential for dynamic imaging. The dual-compressed concept, which transforms unobtrusive spatial difference into spatio-temporal detectable information, can be generalized to other imaging modalities to realize efficient, high-spatial-resolution imaging.

3.
J Cancer Res Clin Oncol ; 149(8): 4639-4651, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36175801

RESUMO

PURPOSE: Serum-derived extracellular vesicles (EVs) have been reported to play an important role in non-small cell lung cancer (NSCLC). The current study sought to explore the effect of serum-EVs delivering m6A methylation regulator heterogeneous nuclear ribonucleoprotein C (HNRNPC) on the development of NSCLC through the regulation of discs large-associated protein 5 (DLGAP5). METHODS: NSCLC-related RNA-Seq and clinical data were first obtained from the TCGA database to screen differentially expressed m6A-related regulators, which were intersected with the differential genes in NSCLC-related microarray GSE43458 obtained from the GEO database for survival analysis and clinical correlation analysis. Correlation between HNRNPC and DLGAP5 expression was evaluated. Serum-EVs were isolated and identified, and the uptake of EVs by A549 cells was visualized using fluorescence microscopy. In vivo xenograft tumor models and tumor metastasis models were constructed in nude mice to observe growth and metastasis of NSCLC cells. RESULTS: HNRNPC was associated with poor prognosis and metastasis of NSCLC, and further implicated in the regulation of DNA replication and cell cycle-related pathways. HNRNPC might promote the growth and metastasis of NSCLC by identifying m6A modification of DLGAP5 mRNA. Serum-EVs delivered HNRNPC to NSCLC cells in vitro. In vivo experimentation further confirmed that serum-EVs could deliver HNRNPC to promote the growth and metastasis of NSCLC cells in nude mice. CONCLUSIONS: Our findings highlight that serum-EVs can deliver HNRNPC to NSCLC cells, wherein HNRNPC recognizes the m6A modification of DLGAP5 mRNA, thus ultimately promoting NSCLC growth and metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metilação , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Camundongos Nus , RNA Mensageiro/genética , Vesículas Extracelulares/metabolismo , Proteínas de Neoplasias/metabolismo
4.
Nano Converg ; 9(1): 36, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35930145

RESUMO

Photosynthesis is the most important biological process on Earth that converts solar energy to chemical energy (biomass) using sunlight as the sole energy source. The yield of photosynthesis is highly sensitive to the intensity and spectral components of light received by the photosynthetic organisms. Therefore, photon engineering has the potential to increase photosynthesis. Spectral conversion materials have been proposed for solar spectral management and widely investigated for photosynthesis by modifying the quality of light reaching the organisms since the 1990s. Such spectral conversion materials manage the photon spectrum of light by a photoconversion process, and a primary challenge faced by these materials is increasing their efficiencies. This review focuses on emerging spectral conversion materials for augmenting the photosynthesis of plants and microalgae, with a special emphasis on their fundamental design and potential applications in both greenhouse settings and microalgae cultivation systems. Finally, a discussion about the future perspectives in this field is made to overcome the remaining challenges.

5.
Hum Mol Genet ; 31(23): 4094-4106, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35848890

RESUMO

High-throughput circular RNA (circRNA) sequencing identified circRNA_001678 (circ_001678) as an upregulated circRNA in non-small cell lung cancer (NSCLC) tissues. Hence, the current study sought to investigate the function and the underlying mechanism of circRNA_001678 in immune escape of NSCLC. Briefly, commercially purchased NSCLC cell lines were adopted for in vitro experiment to evaluate the effects of circ_001678 over-expression or knockdown on cell biological functions, including proliferation, migration and invasive abilities. In addition, the effects of circ_001678 on the in vivo tumorigenicity ability were evaluated for verification. Accordingly, we uncovered that circ_001678 over-expression augmented NSCLC progression in vitro and enhanced tumorigenicity ability in vivo. The interaction between circ_001678 and miR-326 predicted online was verified by means of luciferase and RNA pull-down assays. Furthermore, circ_001678 could sponge miR-326 to up-regulate ZEB1. On the other hand, the tumor-promoting effects of circ_001678 could be inhibited by anti-PD-L1/PD-1 treatment. Mechanistically, circ_001678 led to the activation of the PD-1/PD-L1 pathway to promote CD8+ T cell apoptosis, thereby inducing NSCLC cell immune escape via regulation of the miR-326/ZEB1 axis. To conclude, our findings revealed that circ_001678 sponges miR-326 to up-regulate ZEB1 expression and induce the PD-1/PD-L1 pathway-dependent immune escape, thereby promoting the malignant progression of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Receptor de Morte Celular Programada 1/genética , RNA Circular/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
6.
Ann Palliat Med ; 11(5): 1725-1735, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35672890

RESUMO

BACKGROUND: Metagenomic next-generation sequencing (mNGS) exerts a vital part in accurately diagnosing pulmonary infection. However, the diagnostic value of different samples obtained by virtual bronchoscopic navigation (VBN) combined with mNGS for pathogen detection in infections located in the peripheral lung field (PLF) is still unclear. METHODS: Patients infected from July 2018 to February of the following year were carefully analyzed and divided into two parts, namely, non-infectious disease group and the infectious disease group. Then bronchial expansion tests were performed for each subject, collected liquid specimens and tissue standards, and conducted regular mNGS and microbiological detection and analysis. The value of mNGS and culture in pathogen detection was compared, at the same time, the performance of tissue mNGS and bronchoalveolar lavage fluid (BALF) mNGS in the diagnosis process was compared. When discrete variables were processed, Pearson χ2 and Fisher's exact test could be used to perform categorical variables analysis. Continuous variables were analyzed and compared by Mann-Whitney U test. RESULTS: After mNGS diagnosis, Acinetobacter baumannii, Pseudomonas aeruginosa and Rothia mucilaginosa were the bacterial species showing the highest abundances. In addition, mNGS achieved the sensitivities in the detection of pathogens in tissues and BALF of 72.9% and 81.4%, respectively, and it is higher than conventional culture. Bacterial diagnostic sensitivity was significantly different between BALF and tissue using mNGS (95.0% vs. 62.5%, P=0.03). The sensitivity and specificity of BALF in detecting fungal infections were not significantly different from those of mNGS. A consistency test showed that these two methods had some degree of consistency (k=0.673, P=0.000). CONCLUSIONS: This study showed that the mNGS in BALF samples and the mNGS in tissue samples which could be used to test for pathogens in the lungs. The sensitivity will increase when mNGS is combined with culture. Also, mNGS of BALF and tissues had some degree of consistency to detect fungal infections, whereas mNGS of BALF had better sensitivity to detect bacterial infection than mNGS of tissues.


Assuntos
Doenças Transmissíveis , Micoses , Líquido da Lavagem Broncoalveolar/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão , Micoses/diagnóstico
7.
Artigo em Inglês | MEDLINE | ID: mdl-35565166

RESUMO

Metal mesh devices (MMDs) are novel materials that enable the precise separation of particles by size. Structurally, MMDs consist of a periodic arrangement of square apertures of characteristic shapes and sizes on a thin nickel membrane. The present study describes the separation of aerosol particles using palm-top-size collection devices equipped with three types of MMDs differing in pore size. Aerosols were collected at a farm located in the suburbs of Nairobi, Kenya; aerosol particles were isolated, and pathogenic bacteria were identified in this microflora by next-generation sequencing analysis. The composition of the microflora in aerosol particles was found to depend on particle size. Gene fragments were obtained from the collected aerosols by PCR using primers specific for the genus Mycobacterium. This analysis showed that Mycobacterium obuense, a non-tuberculous species of mycobacteria that causes lung diseases, was present in these aerosols. These findings showed that application of this MMD analytical protocol to aerosol particles can facilitate the investigation of airborne pathogenic bacteria.


Assuntos
Bactérias , Metais , Aerossóis/análise , Bactérias/genética , Quênia , Tamanho da Partícula
8.
Opt Express ; 30(3): 4642-4654, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35209696

RESUMO

In this study, we propose a micro-sized photonic structure that extracts 89% of the intrinsic trapped photons from the spectrum conversion film into free space using the Monte-Carlo ray-tracing method. Furthermore, the spectrum of the spectral-shifting film can be accurately simulated based on a mean free path concept, providing the estimation of its overall performance including the external quantum efficiency and the self-absorption efficiency. The simulations show that the spectrum conversion film with micro-structures shows a two-fold increase in the total external quantum efficiency and a four-fold increase in the external quantum efficiency in the forward viewing direction compared to the planar spectrum conversion films without micro-structures.

9.
Mol Biotechnol ; 64(6): 611-620, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35022995

RESUMO

Overexpression of human dynactin-associated protein (dynAP) transforms NIH3T3 cells. DynAP is a single-pass transmembrane protein with a carboxy-terminal region (amino acids 135-210) exposed to the outside of the cell possessing one potential N-glycosylation site (position 143) and a distal C-terminal region (residues 173-210) harboring a Thr/Ser-rich (T/S) cluster that may be O-glycosylated. In SDS-PAGE, dynAP migrates anomalously at ~ 45 kDa, much larger than expected (22.5 kDa) based on the amino acid composition. Using dynAP mutants, we herein showed that the T/S cluster region is responsible for the anomalous migration. The T/S cluster region is required for transport to the cytoplasmic membrane and cell transformation. We produced and purified the extracellular fragment (dynAP135-210) in secreted form and analyzed the attached glycans. Asn143 displayed complex-type glycosylation, suggesting that oligosaccharide transferase may recognize the NXT/S sequon in the secretory form, but not clearly in full-length dynAP. Core I-type O-glycosylation (Gal-GalNAc) was observed, but the mass spectrometry signal was weak, clearly indicating that further studies are needed to elucidate modifications in this region.


Assuntos
Aminoácidos , Polissacarídeos , Animais , Complexo Dinactina , Glicosilação , Humanos , Camundongos , Células NIH 3T3 , Polissacarídeos/química
10.
Sci Total Environ ; 816: 151582, 2022 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-34785215

RESUMO

The Yellow River Estuary and Laizhou Bay are located on the northern Shandong Peninsula in the Bohai Sea in China and have been polluted by intensive anthropogenic activity. However, few studies have focused on the effect of these activities on the microbial communities and their ecological functions in this area. In this study, the combination of 16S rDNA gene sequencing and GeoChip technology was used to analyzed the microbial community component and their functional genes. Thaumarchaeot and Bacteroidetes are the most abundant phyla. The results of correlation analysis and redundancy analysis (RDA) showed water depth (r2 = 0.76, P = 0.005), total Na content (r2 = 0.63, P = 0.021) and total Ca content (r2 = 0.53, P = 0.05) in the sediments were the most significant environmental factors affecting the microbial community. The diversity of the microbial community and signal intensity of functional genes at nearshore sites (N sites) were higher than that at the offshore sites (O sites), but the component of microbial community and functional genes was similar in general. Functional genes for C, N, P and S cycle were detected at both nearshore and offshore sites, which illustrated that microbial communities were active in nutrient cycle. Proteobacteria contributes significantly to material cycle in microbial community. In addition, functional genes related to organic remediation and metal detoxification are also abundant. It indicated that the environmental pollution caused by anthropogenic activities has greatly affected the microbial community components and their biochemical functions in the Yellow River Estuary and surrounding areas. This study reveals the effect of anthropogenic activities on microbial communities and provides the basis for environmental management.


Assuntos
Microbiota , Rios , China , Estuários , Sedimentos Geológicos , Proteobactérias
11.
FEBS Open Bio ; 11(8): 2110-2117, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34043884

RESUMO

Overexpression of human dynactin-associated protein isoform a (dynAPa) transforms NIH3T3 cells. DynAPa is a single-pass transmembrane protein with a carboxy-terminal region exposed to the outside of cells. According to the NCBI RefSeq database, there may be two other splicing variants of the encoding gene (dynAPb and c). DynAPa and c differ in some amino-terminal residues (NH2 -MVA in dynAPa and NH2 -MEYQLL in dynAPc). DynAPb has the same amino-terminal residues as dynAPc, but lacks 55 residues in the intracellular region. All three isoforms have the same carboxy-terminal region, including the transmembrane domain. Expression of mRNAs of three splicing variants was found in human cancer cell lines ACHN and Caki-1. The subcellular localization and in vitro cell transformation ability of the three isoforms were examined using NIH3T3 cells overexpressing each respective isoform. All isoforms were found to be localized to the Golgi apparatus and plasma membrane, where the carboxy-terminal region was exposed to the outside of cells. Cell transformation was tested using focus formation due to loss of contact inhibition of cell proliferation, and colony formation was examined on soft agar and spheroid formation in ultralow U-bottomed wells. DynAPa robustly formed foci and colonies on soft agar and spheroid, whereas these abilities were considerably decreased for dynAPb and completely lost in dynAPc. These findings warrant dissection studies to identify the dynAP domain that is required for cell transformation.

12.
J Transl Med ; 19(1): 37, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472665

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC. METHODS: Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro. RESULTS: miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development. CONCLUSION: Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Vesículas Extracelulares/metabolismo , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Metiltransferases , Camundongos , MicroRNAs/genética , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína Smad8
14.
Nat Food ; 2(6): 434-441, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37118233

RESUMO

Improving photosynthesis and light capture increases crop yield and paves a sustainable way to meet the growing global food demand. Here we introduce a spectral-shifting microphotonic thin film as a greenhouse envelope that can be scalably manufactured for augmented photosynthesis. By breaking the intrinsic propagation symmetry of light, the photonic microstructures can extract 89% of the internally generated light and deliver most of that in one direction towards photosynthetic organisms. The microphotonic film augments lettuce production by more than 20% in both indoor facilities with electric lighting and in a greenhouse with natural sunlight, offering the possibility of increasing crop production efficiency in controlled environments.

15.
Science ; 370(6518): 786-791, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184205

RESUMO

Photonic materials designed at wavelength scales have enabled a range of emerging energy technologies, from solid-state lighting to efficient photovoltaics that have transformed global energy landscapes. Daytime passive radiative cooling materials shed heat from the ground to the cold universe by taking advantage of the terrestrial thermal radiation that is as large as the renewable solar energy. Newly developed photonic materials permit subambient cooling under direct sunshine, and their applications are expanding rapidly enabled by scalable manufacturing. We review here the recent advancement of daytime subambient radiative cooling materials, which allow energy-efficient cooling and are paving the way toward technologies that harvest the coldness from the universe as a new renewable energy source.

16.
ACS Sens ; 5(6): 1657-1664, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32390428

RESUMO

Surface acoustic wave (SAW) devices are widely used for physical, chemical, and biological sensing applications, and their sensing mechanisms are generally based on frequency changes due to mass-loading effects at the acoustic wave propagation area between two interdigitated transducers (IDTs). In this paper, a new sensing mechanism has been proposed based on a significantly enhanced mass-loading effect generated directly on Au IDT electrodes, which enables significantly enhanced sensitivity, compared with that of conventional SAW devices. The fabricated ultrahigh-frequency SAW devices show a significant mass-loading effect on the electrodes. When the Au-electrode thickness increased from 12 to 25 nm, the Rayleigh mode resonant frequency decreased from 7.77 to 5.93 GHz, while that of the higher longitudinal leaky SAW decreased from 11.87 to 9.83 GHz. The corresponding mass sensitivity of 7309 MHz·mm2·µg-1 (Rayleigh mode) is ∼8.9 × 1011 times larger than that of a conventional quartz crystal balance (with a frequency of 5 MHz) and ∼1000 times higher than that of conventional SAW devices (with a frequency of 978 MHz). Trinitrotoluene concentration as low as 4.4 × 10-9 M (mol·L-1) can be detected using the fabricated SAW sensor, proving its giant mass-loading effect and ultrahigh sensitivity.


Assuntos
Acústica , Som , Eletrodos , Quartzo , Transdutores
17.
RSC Adv ; 10(33): 19178-19184, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35515426

RESUMO

Surface acoustic wave (SAW) devices based on piezoelectric thin-films such as ZnO and AlN are widely used in sensing, microfluidics and lab-on-a-chip applications. However, for many of these applications, the SAW devices will inevitably be used in acid or alkali harsh environments, which may cause their early failures. In this work, we investigated the behavior and degradation mechanisms of thin film based SAW devices in acid and alkali harsh environments. Results show that under the acid and alkali attacks, chemical reaction and corrosion of ZnO devices are very fast (usually within 45 s). During the corrosion, the crystalline orientation of the ZnO film is not changed, but its grain defects are significantly increased and the grain sizes are decreased. The velocity of ZnO-based SAW devices is decreased due to the formation of porous structures induced by the chemical reactions. Whereas an AlN thin-film based SAW device does not perform well in acid-alkali conditions, it might be able to maintain a normal performance without obvious degradation for more than ten hours in acid or alkali solutions. This work could provide guidance for the applications of both ZnO or AlN-based SAW devices in acid/alkali harsh environments.

18.
Mol Ther Nucleic Acids ; 18: 166-182, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31557618

RESUMO

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular progress in lung adenocarcinoma. In this study, to identify cancer-related lncRNAs and genes, we screened for those lncRNAs that were differentially expressed in lung adenocarcinoma, which revealed LINC00628 overexpression and low expression of laminin subunit alpha 3 (LAMA3). This was further validated in the cancerous tissues from patients diagnosed with lung adenocarcinoma. Thereafter, we explored the functional relevance of LINC00628 and LAMA3 in lung adenocarcinoma by analyzing the recruitment of DNA methyltransferase (DNMT) and the cellular processes of lung adenocarcinoma cells following treatments that induced LINC00628 overexpression or LINC00628 silencing or with 5-azacytidine (5-Aza, a DNMT inhibitor). The results showed that LINC00628 silencing decreased cell proliferation, migration, and invasion as well as the drug resistance of lung adenocarcinoma cells to vincristine (VCR). The results were opposite in the cells with LAMA3 demethylation induced by 5-Aza treatment. Further research indicated that LINC00628 recruited DNMT1, DNMT3A, and DNMT3B to promote the methylation of LAMA3 promoter, thereby decreasing its expression. Moreover, an in vivo experiment was performed in nude mice to assess the tumor growth ability and drug resistance of human lung adenocarcinoma cells. It was observed that LINC00628 silencing or 5-Aza treatment inhibited the in vivo tumor growth ability of the human lung adenocarcinoma cells and reduced their resistance to VCR. Altogether, our results provide evidence of a mechanism by which LINC00628 silencing exerts an inhibitory role in lung adenocarcinoma by modulating the DNA methylation of LAMA3, indicative of a novel molecular target for treatment of lung adenocarcinoma patients showing resistance to VCR.

19.
J Cell Mol Med ; 23(9): 6411-6428, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31317666

RESUMO

Lung adenocarcinoma is a common histologic type of lung cancer with a high death rate globally. Increasing evidence shows that long non-coding RNA H19 (lncRNA H19) and CDH1 methylation are involved in multiple tumours. Here, we tried to investigate whether lncRNA H19 or CDH1 methylation could affect the development of lung adenocarcinoma. First, lung adenocarcinoma tissues were collected to detect CDH1 methylation. Then, the regulatory mechanisms of lncRNA H19 were detected mainly in concert with the treatment of overexpression of lncRNA H19, siRNA against lncRNA H19, overexpression of CDH1 and demethylating agent A-5az in lung adenocarcinoma A549 cell. The expression of lncRNA H19 and epithelial-mesenchymal transition (EMT)-related factors as well as cell proliferation, sphere-forming ability, apoptosis, migration and invasion were detected. Finally, we observed xenograft tumour in nude mice so as to ascertain tumorigenicity of lung adenocarcinoma cells. LncRNA H19 and methylation of CDH1 were highly expressed in lung adenocarcinoma tissues. A549 cells with silencing of lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation by demethylating agent 5-Az had suppressed cell proliferation, sphere-forming ability, apoptosis, migration and invasion, in addition to inhibited EMT process. Silencing lncRNA H19 could reduce methylation level of CDH1. In vivo, A549 cells with silencing lncRNA H19, overexpression of CDH1 or reduced CDH1 methylation exhibited low tumorigenicity, reflected by the smaller tumour size and lighter tumour weight. Taken together, this study demonstrates that silencing of lncRNA H19 inhibits EMT and proliferation while promoting apoptosis of lung adenocarcinoma cells by inhibiting methylation of CDH1 promoter.


Assuntos
Adenocarcinoma de Pulmão/genética , Antígenos CD/genética , Caderinas/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , Células A549 , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Metilação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Adulto Jovem
20.
Soft Matter ; 15(18): 3740-3750, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31042253

RESUMO

A spiropyran-containing triazole-phosphatidylcholine (SPTPC) was synthesized through a copper-catalyzed azide alkyne cyclo-addition (CuAAC) reaction. In water, SPTPCs self-assembled and a spontaneous spiropyran-to-merocyanine (SP-to-MC) isomerization occurred, resulting in coexistence of liposomes and fibers, and switching from the spiropyran (SP) to the merocyanine (MC) isomeric structure induced a reversible transition between these molecular assemblies. Study of the self-assembly of SPTPCs and photo-induced liposome-fiber assembly-transition revealed that the presence of MC enabled additional inter-membrane interaction during self-assembly and that the MC-stacking effect was the driving force for the assembly-transition. Exposure to UV light induced switching from SP to MC, where the planar structure of MC and the confinement of MC led to enhanced MC-stacking. The effect of MC-stacking was both advantageous and disadvantageous: MC-stacking perturbed the hydrophobic phase in the bilayer membrane and facilitated the liposome-to-fiber transition, otherwise the MC-stacking retarded switching of MC to SP, and caused an incomplete recovery of MC to SP during fiber-to-liposome recovery, thus a fatigue of SP was induced by MC-stacking during the liposome-to-fiber transition cycle. To decrease the intermolecular interactions and suppress MC-stacking, photo-inert triazole-phosphatidylcholine (TPC) was incorporated to prepare two-component TPC/SPTPC-liposomes, which exhibited better recovery kinetics. The photo-adaptive behavior of TPC/SPTPC-liposomes confirmed the disturbance of bilayer membranes by inter-membrane MC-stacking and the formation of MCTPC-enriched phases in the bilayer membrane.


Assuntos
Benzopiranos/química , Indóis/química , Lipossomos/química , Nitrocompostos/química , Fosfatidilcolinas/química , Processos Fotoquímicos , Triazóis/química , Alcinos/química , Azidas/química , Catálise , Cobre/química , Bicamadas Lipídicas/química , Transição de Fase , Raios Ultravioleta
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