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1.
Opt Lett ; 45(7): 1998-2001, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236052

RESUMO

Optofluidic manipulation of droplets is critical in droplet-based microfluidic systems for chemistry, biology, and medicine. Here, we reported a thermocapillary microvortices-based manipulation platform for controlling oil-in-water droplets through integrating a photothermal waveguide into a microfluidic chip. The sizes and shapes of the droplets can be controlled by adjusting optical power or positions of the water-oil interface. Here, teardrop-shaped droplets, which can encapsulate and accumulate mesoscopic matters easily, were generated when the water-oil interface and the channel boundaries approached the photothermal waveguide center simultaneously. The results showed that the thermocapillary microvortices have good controllability of droplet positions, droplet volumes, and encapsulated-particle distribution and thus it will be a powerful droplet manipulation strategy for microreactors and microcapsules.

2.
ACS Sens ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32181650

RESUMO

For the first time, a reproducible surface plasmon-enhanced optical sensor for the detection of gaseous formaldehyde was proposed, which was fabricated by depositing a mixture of CdSe@ZnS quantum dots (QDs), fumed silica (FS), and gold nanoparticles (GNs) on the surface of a silica sphere array to meet the urgent requirement of a rapid, sensitive, and highly convenient formaldehyde detection method. Because of the spectral overlap between QDs and GNs, plasmon-enhanced fluorescence was observed in the film of QDs/FS/GNs. When exposed to formaldehyde molecules, the enhanced fluorescence was quenched linearly with the increase of formaldehyde concentration in the range of 0.5-2.0 ppm. The reason is attributed to the nonradiative electron transfer from QDs to the carbonyl of formaldehyde molecules with the assistance of amino groups. Our results demonstrate that the designed sensors are capable of detecting ultralow concentration gaseous formaldehyde at room temperature with a fast response-recovery time and excellent selectivity, stability, and reproducibility. This work provides a simple and low-cost approach for optical formaldehyde sensor fabrication and shows promising applications in environmental detection.

3.
Cancer Res ; 80(3): 406-417, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32015157

RESUMO

Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complexes have a mutation rate of approximately 20% in human cancer, and ARID1A is the most frequently mutated component. However, some components of SWI/SNF complexes, including ARID1A, exhibit a very low mutation rate in squamous cell carcinoma (SCC), and their role in SCC remains unknown. Here, we demonstrate that the low expression of ARID1A in SCC is the result of promoter hypermethylation. Low levels of ARID1A were associated with a poor prognosis. ARID1A maintained transcriptional homeostasis through both direct and indirect chromatin-remodeling mechanisms. Depletion of ARID1A activated an oncogenic transcriptome that drove SCC progression. The anti-inflammatory natural product parthenolide was synthetically lethal to ARID1A-depleted SCC cells due to its inhibition of both HDAC1 and oncogenic signaling. These findings support the clinical application of parthenolide to treat patients with SCC with low ARID1A expression. SIGNIFICANCE: This study reveals novel inactivation mechanisms and tumor-suppressive roles of ARID1A in SCC and proposes parthenolide as an effective treatment for patients with SCC with low ARID1A expression.

4.
Cancer Lett ; 469: 390-398, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31730904

RESUMO

Metastasis is a major lethal cause of esophageal squamous cell carcinoma (ESCC) and confers a poor prognosis. Previous studies demonstrated that serpin family E member 2 (SERPINE2) is involved in tumor metastasis. However, the function and mechanism of SERPINE2 in ESCC metastasis remains unclear. In this study, we found that SERPINE2 was increased in ESCC and associated with tumor metastasis. SERPINE2 knockdown inhibited tumor cell invasion and lymph node and lung metastasis by inducing epithelial-mesenchymal transition (EMT). We identified a total of 410 differentially expressed genes in SERPINE2-knockdown cells by RNA-Seq analysis. Among them, bone morphogenetic protein 4 (BMP4) was significantly downregulated. Conversely, BMP4 was increased in SERPINE2-overexpressing cells. Inhibiting BMP4 could attenuate SERPINE2-induced migration and invasion. Moreover, SERPINE2 was positively correlated with clinical stage, tumor invasion depth and lymph node metastasis in ESCC patients. These findings suggest that SERPINE2 promotes tumor metastasis by activating BMP4 and could serve as a potential therapeutic target for clinical intervention in ESCC.

5.
Int J Med Sci ; 16(12): 1642-1651, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839752

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer without effective targeted drugs. While breast cancer patients often use acupuncture for the relief of cancer-induced pain or the side effects of chemo- or radiation therapy, little information is known regarding the direct effects of electroacupuncture on TNBC tumor and its potential mechanisms. Here, we created a mice model of TNBC and electroacupuncture with encircled needling around the tumors was given to the animals daily for 3 weeks at 15-20 Hz (3 min, each time). For sham electroacupuncture control, the skin was punctured to a depth of 5 mm and then the needle was quickly withdrawn without electrical stimulation or manual needle manipulation. We found that electroacupuncture significantly inhibited TNBC tumor growth and the inhibitory rate increased gradually overtime. Mechanistic analysis showed that electroacupuncture inhibited tumor angiogenesis by reducing the expression of vascular endothelial growth factor A (VEGF-A), its receptor VEGF-R and neuropilin 1 (NRP-1). Electroacupuncture also led to a significant decrease of matrix metalloproteinase-2 (MMP-2) expression and an increase of tissue inhibitor of MMP (TIMP-2) expression. Additionally, the expression of semaphorin 3A (Sema3A) and nerve growth factor receptor (NGFR) p75 in TNBC tissue was significantly upregulated in response to electroacupuncture. Furthermore, tumor necrosis factor (TNF)-alpha level in the serum was dramatically reduced after electroacupuncture. These results showed that electroacupuncture could directly inhibit TNBC tumor growth through the inhibition of proteins related to tumor angiogenesis and extracellular matrix, the suppression of TNBC-induced inflammation and the upregulation of nerve growth factor receptors.

6.
Opt Express ; 27(20): 28507-28522, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684601

RESUMO

Pulsating behavior is a universal phenomenon in versatile fields. In nonlinear dissipative systems, the solitons also pulsate under proper conditions and show many interesting dynamics. However, the pulsation dynamics are generally concerned with single-soliton cases. Herein, by utilizing real-time spectroscopy technique, namely, dispersive Fourier-transform (DFT), we reveal the distinct dynamical diversity of pulsating solitons in a fiber laser. In particular, the weak to strong explosive behaviors of pulsating solitons, as well as the rogue wave generation during explosions are observed. Moreover, the concept of soliton pulsation is extended to the multi-soliton case. It is found that the simultaneous pulsations of energy, separation and relative phase difference could be observed for solitons inside the molecule, while the pulsations of each individual in a multi-soliton bunch could be regular or irregular. These findings will shed new insights into the complex nonlinear behavior of solitons in ultrafast fiber lasers as well as dissipative optical systems.

7.
Opt Lett ; 44(7): 1868-1871, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30933168

RESUMO

In advanced biomedicine and microfluidics, there is a strong desire to sort and manipulate various cells and bacteria based on miniaturized microfluidic chips. Here, by integrating fiber tweezers into a T-type microfluidic channel, we report an optofluidic chip to selectively trap Escherichia coli in human blood solution based on different sizes and shapes. Furthermore, we simulate the trapping and pushing regions of other cells and bacteria, including rod-shaped bacteria, sphere-shaped bacteria, and cancer cells based on finite-difference analysis. With the advantages of controllability, low optical power, and compact construction, the strategy may be possibly applied in the fields of optical separation, cell transportation, and water quality analysis.


Assuntos
Separação Celular/instrumentação , Miniaturização/instrumentação , Fibras Ópticas , Pinças Ópticas , Animais , Desenho de Equipamento , Eritrócitos/microbiologia , Escherichia coli/citologia , Humanos
8.
Oncogene ; 38(25): 4990-5006, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30858545

RESUMO

Cancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse. However, it remains unclear whether specific miRNAs have direct roles in radioresistance and/or prognosis. In this study, we find that miR-339-5p promotes radiosensitivity, and is downregulated in radioresistant subpopulations of esophageal cancer cells. Notably, miR-339-5p was selectively secreted into blood via exosomes, and that higher serum miR-339-5p levels were positively associated with radiotherapy sensitivity and good survival. Moreover, miR-339-5p expression was downregulated in the T3/T4 stage compared with T1/T2 stage in esophageal squamous cell carcinoma (ESCC) patients (P = 0.04), and low miR-339-5p expression in tissue was significantly associated with poor overall survival (P = 0.036) and disease-free survival (P = 0.037). Overexpression of miR-339-5p enhanced radiosensitivity in vitro and in vivo. Mechanistically, miR-339-5p enhances radiosensitivity by targeting Cdc25A, and is transcriptionally regulated by Runx3. Correlations were observed between miR-339-5p levels and Cdc25A/Runx3 levels in tissue samples. Intriguingly, combined analysis of miR-339-5p expression with Runx3 increased the separation of the survival curves obtained for either gene alone in the TCGA datasets (P = 0.009). Overall, exosome-derived miR-339-5p mediates radiosensitivity through downregulation of Cdc25A, and predicts pathological response to preoperative radiotherapy in locally advanced ESCC, suggesting it could be a promising non-invasive biomarker for facilitating personalized treatments.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs/fisiologia , Tolerância a Radiação/genética , Fosfatases cdc25/genética , Animais , Biomarcadores Tumorais/fisiologia , Linhagem Celular Tumoral , Progressão da Doença , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/radioterapia , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Prognóstico
9.
Curr Pharm Des ; 25(8): 862-870, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30848190

RESUMO

BACKGROUND AND OBJECTIVE: Bevacizumab (BVZ) is a recombinant humanized antibody that inhibits the vascular endothelial growth factor A (VEGFA) and is used for the treatment of various types of cancer. BVZ is primarily given by the intravenous drip (I.V.), which often leads to low efficacy and various side effects. Therefore, the present study was to evaluate the effect of local delivery of BVZ against triple-negative breast cancer (TNBC) xenograft tumors. METHODS: Mice 4T1 TNBC cells were engrafted in female BALB/c mice. After the tumors reached about 5 mm (diameter), animals were treated with BVZ through the local injection from four directions around the tumors. The tumor growth, survival and potential mechanisms of action were evaluated. RESULTS: The growth and microvessel density of engrafted tumors were dramatically reduced with the tumor inhibition rate of 32.8 ± 3%. No obvious side effects were observed. The expression of VEGFA, VEGF receptor (VEGFR), matrix metalloproteinase (MMP)-2, MMP-9, Delta-like ligand 4 (DLL4) and Integrin-5 was significantly reduced in TNBC tumor tissues. In contrast, tissue inhibitor of matrix metalloproteinase (TIMP)-2 was significantly upregulated in xenograft tumors. Additionally, local delivery of BVZ led to the reduction of VEGFA and tumor necrosis factor (TNF)-alpha in the serum. Protein-protein interaction (PPI) analysis revealed that the proteins altered by the local delivery of BVZ were associated with angiogenesis and regulation of cell migration. CONCLUSION: This study provided evidence associated with local delivery of BVZ against TNBC tumors supporting the use of BVZ local injections to overcome some of the disadvantages associated with I.V. therapy with BVZ.


Assuntos
Bevacizumab/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados , Linhagem Celular Tumoral , Feminino , Injeções , Camundongos , Camundongos Endogâmicos BALB C , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
10.
J Cell Biochem ; 120(4): 5207-5217, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30320451

RESUMO

Radiotherapy plays a crucial role in combined treatment modality in local advanced rectal cancer (LARC). While neoadjuvant chemoradiotherapy responses were variable in LARC patients, so, it is important to identify genes that closely associated with short-term and long-term responses to radiotherapy. In this study, we profiled long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression values of LARC patients with different neoadjuvant chemoradiotherapy downstaging depth score based on Agilent Arraystar Human LncRNA V3.0 Array(Agilent, CA). LncRNAs and mRNAs with aberrant expression values between the two groups of LARC patients were identified and lncRNA-miRNA-mRNA regulation network was also obtained through the combination of miRcode and miRTarBase database. Gene interaction network and module analysis of differential expression mRNAs contained in the lncRNA-miRNA-mRNA network identified five hub genes, including KRAS, PDPK1, PPP2R5C, PPP2R1B, and YES1, that should be closely associated with LARC's response to chemoradiotherapy. Besides, Kaplan-Meier analysis based on the Cyber Research Center (CRC) data set from The Cancer Genome Atlas indicated that aberrant expression of the five hub genes is significantly associated with CRC overall survival. In conclusion, we obtained several biomarkers that should be associated with neoadjuvant chemoradiotherapy response in LARC, which should be helpful for individual treatment and prognosis improvement.

11.
Opt Lett ; 43(24): 5965-5968, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30547981

RESUMO

We reported, to the best of our knowledge, the first experimental evidence of the pulsating soliton with chaotic behavior in an ultrafast fiber laser. By virtue of a dispersive Fourier transformation method, the chaotic behavior of soliton pulsation is visualized by the fact that the mode-locked spectrum collapses abruptly in an unpredictable way during the pulsating process. The obtained results provide the experimental demonstration of the chaotic behavior in the pulsating soliton, which would also give some new insights into the soliton pulsation dynamics in dissipative systems.

12.
Opt Express ; 26(14): 17804-17813, 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-30114065

RESUMO

We experimentally report the coexistence of the rectangular noise-like pulse (NLP) and the Gaussian-shape NLP in a figure-eight fiber laser. Benefiting from the strengthened nonlinear effect of a segment of highly nonlinear fiber (HNLF) in the cavity, the coexistent NLPs with various patterns, i.e. one rectangular pulse with one Gaussian-shape pulse, one rectangular pulse with two Gaussian-shape pulses and two rectangular pulses with one Gaussian-shape pulse, are formed depending on the cavity parameters setting. In particular, the evolution of these coexistent NLPs properties with pump power is investigated. It is found that the duration of the rectangular pulse always increases, while the Gaussian-shape pulse has almost no changes with the increasing pump power. The achieved results demonstrated for the first time, to the best of our knowledge, the pulses with different shapes can coexist under the NLP regime, which contributes to further understanding the fundamental characteristics of the NLPs and multiple pulses.

13.
Opt Express ; 26(3): 2972-2982, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29401830

RESUMO

Taking advantage of technology of spatio-temporal reconstruction and dispersive Fourier transform (DFT), we experimentally observed the buildup dynamics of dissipative soliton in an ultrafast fiber laser in the net-normal dispersion regime. The soliton buildup dynamics were analyzed in both the spectral and temporal domains. We firstly revealed that the appearing of the spectral sharp peaks with oscillation structures during the mode-locking transition is caused by the formation of structural dissipative soliton. The experimental results were explained by the numerical simulations. These findings would give some new insights into the dissipative soliton buildup dynamics in ultrafast fiber lasers.

14.
Cancer Res ; 78(4): 1069-1082, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29233925

RESUMO

A competent DNA damage response (DDR) helps prevent cancer, but once cancer has arisen, DDR can blunt the efficacy of chemotherapy and radiotherapy that cause lethal DNA breakage in cancer cells. Thus, blocking DDR may improve the efficacy of these modalities. Here, we report a new DDR mechanism that interfaces with inflammatory signaling and might be blocked to improve anticancer outcomes. Specifically, we report that the ubiquitin-editing enzyme A20/TNFAIP3 binds and inhibits the E3 ubiquitin ligase RNF168, which is responsible for regulating histone H2A turnover critical for proper DNA repair. A20 induced after DNA damage disrupted RNF168-H2A interaction in a manner independent of its enzymatic activity. Furthermore, it inhibited accumulation of RNF168 and downstream repair protein 53BP1 during DNA repair. A20 was also required for disassembly of RNF168 and 53BP1 from damage sites after repair. Conversely, A20 deletion increased the efficiency of error-prone nonhomologous DNA end-joining and decreased error-free DNA homologous recombination, destablizing the genome and increasing sensitivity to DNA damage. In clinical specimens of invasive breast carcinoma, A20 was widely overexpressed, consistent with its candidacy as a therapeutic target. Taken together, our findings suggest that A20 is critical for proper functioning of the DDR in cancer cells and it establishes a new link between this NFκB-regulated ubiquitin-editing enzyme and the DDR pathway.Significance: This study identifies the ubiquitin-editing enzyme A20 as a key factor in mediating cancer cell resistance to DNA-damaging therapy, with implications for blocking its function to leverage the efficacy of chemotherapy and radiotherapy. Cancer Res; 78(4); 1069-82. ©2017 AACR.


Assuntos
Dano ao DNA , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/farmacologia , Células HEK293 , Células HeLa , Humanos , Células MCF-7 , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias/metabolismo , Regiões Promotoras Genéticas , Transdução de Sinais , Transfecção , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Regulação para Cima
15.
Opt Lett ; 42(21): 4517-4520, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29088202

RESUMO

We report on the switchable generation of a rectangular noise-like pulse (NLP) and a dissipative soliton resonance (DSR) in a fiber laser with highly nonlinear effect at very low pump power. The NLP centered at 1530.5 nm demonstrates a new characteristic that its profile evolves gradually from rectangular shape to Gaussian-like shape with the increasing pump power. By appropriately manipulating the polarization controller (PC), the laser switches emit a DSR pulse centered at 1551.3 nm. The duration of the DSR could broaden from 17.4 ns to the cavity round trip time with increasing the pump power, while keeping the pulse profile and the intensity unaltered. This type of fiber laser may not only facilitate further investigations of the characteristics of NLP and DSR but also serve as a multi-functional optical source for potential applications.

16.
Opt Express ; 25(17): 20923-20931, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041768

RESUMO

We experimentally demonstrate the generation of dissipative soliton resonance (DSR) in a passively mode-locked Bi-doped fiber ring laser based on nonlinear polarization rotation (NPR) technique. The DSR with the central wavelength of 1169.5 nm has a repetition rate of 343.7 kHz. By purely increasing the pump power, the DSR evolves from Gaussian shape to rectangular shape with the duration extending from 2.1 ns to 13.1 ns, while keeping the pulse amplitude and the 3-dB spectrum bandwidth almost constant. The single-pulse energy reaches 24.82 nJ. Furthermore, we construct a lumped model to reproduce the mode-locking process and the traits of the DSR pulse. The obtained results indicate that it could achieve higher pulse energy in mode-locked Bi-doped fiber laser by generating DSR.

17.
Opt Express ; 25(14): 16291-16299, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28789136

RESUMO

We demonstrate a tunable and switchable dual-waveband 100 GHz high-repetition-rate (HRR) ultrafast fiber laser based on dissipative four-wave-mixing (DFWM) mode-locked technique. Each waveband maintains HRR operation. The DFWM effect was realized by combining a Fabry-Perot (F-P) filter and a piece of highly nonlinear fiber (HNLF). The tunable and switchable operations were achieved by nonlinear polarization rotation (NPR) technique. Through appropriately controlling the filtering effect induced by NPR, the laser could operate at two kinds of tunable regimes. One is that the spacing between these two wavebands could be tuned while keeping their center at 1559 nm. The other is that the central position of the entire dual-waveband is tunable while with the same separation between these two wavebands of 13.2 nm. Moreover, the laser could switch between these two wavebands. Correspondingly, the center of the single-waveband has a tuning range of 15.2 nm. This versatile ultrafast fiber laser may find applications in fields of optical frequency combs, high speed optical communications, where HRR pulses are necessary.

18.
Cancer Lett ; 398: 37-45, 2017 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-28408353

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive tumors in Asia. Recent researches demonstrate that miRNAs are involved in the development of ESCC. In this study, we identified a miRNA cluster, termed miR-99b/let-7e/miR-125a as pro-metastasis oncomir. Overexpression of this miRNA cluster promoted ESCC cell migration and invasion in vitro and induced an experimental metastasis in vivo. ZEB1 was discovered to bind to the promoter region of miR-99b/let-7e/miR-125a cluster and regulate the expression of miRNAs at transcriptional level. Knockdown of ZEB1 resulted in a decrease of both mature and primary miRNAs. Further research revealed AT-rich interaction domain 3A (ARID3A) as a direct target of miR-99b/let-7e/miR-125a cluster. Reduced ARID3A phenocopied miR-99b/let-7e/miR-125a overexpression, and elevated ARID3A counteracted the pro-metastasis effect of miR-99b/let-7e/miR-125a. Moreover, ARID3A was downregulated by ZEB1 in a miR-99b/let-7e/miR-125a dependent manner. Collectively, our study sheds light on the essential role of miR-99b/let-7e/miR-125a cluster in tumor metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Movimento Celular , Neoplasias Esofágicas/genética , MicroRNAs/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Animais , Sítios de Ligação , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos SCID , MicroRNAs/metabolismo , Invasividade Neoplásica , Regiões Promotoras Genéticas , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição Genética , Transfecção , Carga Tumoral , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
19.
EBioMedicine ; 15: 48-61, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28040451

RESUMO

The emerging regulatory role of deubiquitinases (DUBs) has been implicated in various fundamental processes and pathogenesis. To determine the pivotal role that DUBs play in mediating tumorigenesis, we have performed a non-biased screen of 67 human DUBs based on a mammary cell transformation assay. This led to the identification of USP11 as a critical determinant of mammary tumor initiation and progression. Using an approach of protein complex purification coupled with mass spectrometry, we further identified XIAP to be a target for USP11. We demonstrated that, while depletion of XIAP attenuates cell transformation, elevated USP11 significantly promotes the tumor colony formation through stabilization of XIAP. Molecular modeling coupled with mutagenesis analyses further revealed that Leu207 on the BIR2 domain of XIAP facilitates its interaction with USP11. Stabilization of XIAP due to its deubiquitylation by USP11 leads to the inhibition of cell anoikis and apoptosis, which in turn promotes tumorigenesis. Finally, immunohistochemical staining revealed that aberrant accumulation of USP11 correlates with elevated levels of XIAP in breast cancer tissues. We therefore propose that aberrant USP11, via stabilization of XIAP, promotes tumor initiation and progression.


Assuntos
Transformação Celular Neoplásica/metabolismo , Tioléster Hidrolases/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Anoikis/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Modelos Biológicos , Modelos Moleculares , Prognóstico , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteólise , Tioléster Hidrolases/química , Ubiquitinação , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/química , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
20.
Opt Lett ; 42(2): 330-333, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28081105

RESUMO

Ultrafast fiber laser, as a dissipative nonlinear optical system, plays an important role in investigating various nonlinear phenomena and soliton dynamics. Vector features of solitons, including polarization locked and polarization rotation vector solitons (PRVSs), are interesting nonlinear dynamics in ultrafast fiber lasers. Herein, we experimentally reveal the trapping characteristics of PRVSs for the first time, to the best of our best knowledge. We show that, for the conventional soliton trapping in the ultrafast fiber laser, the soliton central wavelengths of the two polarization components are constant at the laser output port. However, it is found that the dynamic trapping can be observed for the PRVS. That is, the peak frequencies along the two orthogonal polarization directions are dynamically alternating, depending on the relative intensities of the two polarization components. The obtained results would further unveil the physical mechanism of PRVSs.

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