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1.
Shanghai Kou Qiang Yi Xue ; 30(3): 268-272, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34476443

RESUMO

PURPOSE: To investigate the correlation of clinicopathologic factors and immunophenotypic features with betel nut chewing in oral squamous cell carcinoma(OSCC). METHODS: The data of 88 patients with OSCC were collected. According to the habit of betel nut chewing, the clinicopathologic factors and immunohistochemical parameters were analyzed. The relationship between clinicopathologic factors of OSCC and betel nut chewing was analyzed with univariate analysis and multivariate analysis using SPSS 17.0 software package. RESULTS: 46.6% of patients had the habit of betel nut chewing and 67.0% of patients had tongue cancer and buccal cancer. The pathological stages were mainly T2 (40.9%). From univariate analysis of the results, differentiation degree, ki-67, p53 was significantly correlated with the habit of betel nut chewing(P<0.05); while gender, age, location, pathological T stage and cervical lymph node metastasis were not significantly correlated with habit of betel nut chewing (P>0.05). From multivariate analysis of the results, location and differentiation degree were significantly correlated with the habit of betel nut chewing (P<0.05). CONCLUSIONS: ki-67 and p53 protein are lowly expressed in OSCC patients with the habit of betel nut chewing, suggesting that clinicopathologic factors such as the proliferation activity, malignancy, differentiation and prognosis of tumor are much better. Differentiation degree are relatively good in OSCC patients with the habit of betel nut chewing. Cheek and tongue are the most common site of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Areca/efeitos adversos , Humanos , Mastigação , Carcinoma de Células Escamosas de Cabeça e Pescoço
4.
Environ Pollut ; 288: 117966, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34435561

RESUMO

Microcystins (MCs) produced by cyanobacteria are potent toxins to humans that cannot be ignored. However, the toxicity of MCs to humans remains largely unknown. The study explored the role of MCs in the development of hematological parameters through human observations and a chronic mouse model to explore related mechanisms. The adjusted odds ratio of MC-LR to the risk of anemia was 4.954 (95 % CI, 2.423-10.131) in a case-control study in Nanjing. An inverse correlation between serum MC-LR and hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), and red blood cell count (RBC) was observed. MC-LR in the serum of the population was an independent risk factor for microcytic anemia. Animal experiments demonstrated that MC-LR resulted in microcytic anemia, which is associated with inflammation, dysregulation of iron homeostasis, and erythropoiesis. We first identified the possible signaling pathway of MC-LR-induced anemia that MC-LR significantly upregulated the levels of hepcidin via EPO/EPOR signaling pathway and the decreased levels of Twsg1 and Gdf15, thereby resulting in the decreased levels of Hbb and Fpn, and the increased expression of Fth1, and Tf in a chronic mouse model. Our study first identified that prolonged environmental exposure to MCs probably contribute to the occurrence of microcytic anemia in humans, which provides new insights into the toxicity of MCs for public health.


Assuntos
Anemia Hipocrômica , Anemia , Cianobactérias , Anemia/induzido quimicamente , Animais , Estudos de Casos e Controles , Homeostase , Humanos , Camundongos , Microcistinas
5.
J Alzheimers Dis ; 83(3): 1187-1198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34420964

RESUMO

BACKGROUND: Evidence has emerged that anemia is associated with dementia, but data on the relationships of red blood cell distribution width (RDW) with dementia and cognitive function in older adults are sparse. OBJECTIVE: We sought to investigate the associations of RDW with dementia and global cognitive performance among rural-dwelling Chinese older adults and further to examine their associations by anemia status. METHODS: This population-based cross-sectional study included 5,115 participants (age≥65 years, 57.0%women) in the baseline examination (March-September 2018) of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-CHINA). We collected data through face-to-face interviews, clinical examinations, and laboratory tests. Global cognitive function was evaluated using the Mini-Mental State Examination (MMSE). We defined dementia, Alzheimer's disease (AD), and vascular dementia (VaD) following the respective international criteria. Data were analyzed using multinomial logistic and general linear regression models. RESULTS: Of all participants, 300 were diagnosed with dementia, including 195 with AD and 95 VaD. The multiple-adjusted odds ratio of dementia associated with quartiles of RDW were 1.45 (95%CI: 0.87-2.44), 1.00 (reference), 1.77 (1.07-2.93), and 2.28 (1.40-3.72). Similar J-shaped patterns existed for the association of RDW with odds ratio of AD and VaD. Anemia was not significantly associated with dementia. The J-shaped associations of RDW with dementia and subtypes were statistically evident only among participants without anemia. There was an inverted J-shaped relationship between RDW quartiles and ß-coefficients of MMSE score. CONCLUSION: There is a J-shaped association between RDW level and likelihood of dementias among rural-dwelling Chinese older adults, especially among people without anemia.

6.
Theranostics ; 11(16): 7640-7657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335955

RESUMO

Background: Since primary prostate cancer (PCa) can advance to the life-threatening metastatic PCa, exploring the molecular mechanisms underlying PCa metastasis is crucial for developing the novel targeted preventive strategies for decreasing the mortality of PCa. RNA N6-methyladenosine (m6A) is an emerging regulatory mechanism for gene expression and its specific roles in PCa progression remains elusive. Methods: Western blotting, quantitative real-time PCR and immunohistochemical analyses were used to detect target gene expression in PCa cells in vitro and prostate tissues from patients. RNA immunoprecipitation was conducted to analyze the specific binding of mRNA to the target protein. Migration and invasion assays were used to assess the migratory capacities of cancer cells. The correlation between target gene expression and survival rate of PCa patients was analyzed based the TCGA database. Results: We found that total RNA N6-methyladenosine (m6A) modification levels were markedly upregulated in human PCa tissues due to increased expression of methyltransferase like 3 (METTL3). Further studies revealed that the migratory and invasive capacities of PCa cells were markedly suppressed upon METTL3 knockdown. Mechanistically, METTL3 mediates m6A modification of USP4 mRNA at A2696, and m6A reader protein YTHDF2 binds to and induces degradation of USP4 mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells. Conclusions: Our findings highlight the role of METTL3 in modulating invasion and metastasis of PCa cells, providing insight into promising therapeutic strategies for hindering PCa progressing to deadly metastases.


Assuntos
Metiltransferases/genética , Neoplasias da Próstata/metabolismo , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica/fisiologia , Humanos , Masculino , Metiltransferases/metabolismo , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/metabolismo , Proteases Específicas de Ubiquitina/genética
7.
Front Surg ; 8: 693774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447783

RESUMO

We retrospectively analyzed the diagnosis and treatment process of one patient with recurrent undifferentiated pleomorphic sarcoma (UPS) of infratemporal fossa and made a definite diagnosis by combining the imaging and pathological examination results. After treatment failure with 2 cycles of chemotherapy and several surgeries, UPS was eventually treated by surgery + carbon ion radiotherapy, and MRI reexamination showed no relapse. Head and neck UPS is located deeply, easily recurs after operation, and difficult to be resected completely by surgery, with a gradually shortened interval of relapse over the number of surgeries, which becomes a treatment challenge. After the last surgery, the patient received carbon ion radiotherapy, with a good therapeutic effect, and no sign of relapse just before sending this article. Based on the above advantages, we have concluded that surgery + carbon ion radiotherapy is a new effective pathway to treat head and neck UPS.

8.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34368873

RESUMO

Homocysteine (Hcy) was discovered to be an independent risk factor for the development of atherosclerosis (AS). Moreover, endothelial­mesenchymal transition (EndMT) was found to be one of main mechanisms contributing to the pathogenesis of AS. Salidroside (SAL) has diverse pharmacological activities, including anti­inflammatory, anti­cancer, anti­oxidative and anti­fibrosis properties. However, whether SAL serves a beneficial role in Hcy­induced EndMT remains unknown. The present study aimed to investigate whether SAL exerted its effects on Hcy­induced EndMT via the Kruppel­like factor 4 (KLF4)/endothelial nitric oxide (NO) synthase (eNOS) signaling pathway. HUVECs were pretreated with high and low doses (10 or 50 µmol/l) of SAL for 2 h, followed by 1 mmol/l Hcy for 48 h to induce EndMT. Western blotting was used to analyze the protein expression levels of the endothelial marker, VE­cadherin, the mesenchymal cell marker, α­smooth muscle actin (SMA), and the nuclear transcription factors, KLF4 and eNOS. Wound healing assays were used to determine the cell migratory ability, and the levels of NO in the cell culture supernatants were measured using a nitrate reductase assay. Cellular immunofluorescence was used to analyze the expression and localization of KLF4. Small interfering (si)RNA targeting KLF4 (siKLF4) was used to knock down KLF4 expression in HUVECs. The results of the present study revealed that treatment with SAL upregulated the expression levels of VE­cadherin, downregulated the expression levels of α­SMA, reduced cell migration and activated the eNOS/NO signaling axis, as well as downregulated KLF4 expression and translocation to the nucleus. Compared with the SAL + siKLF4 co­administration group, no significant differences were observed in the expression levels of the phenotypic markers in the SAL or siKLF4 groups. In conclusion, the findings of the present study revealed that SAL may inhibit Hcy­induced EndMT via regulation of the KLF4/eNOS signaling pathway.

9.
Sci Total Environ ; 794: 148732, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34323745

RESUMO

It has been reported that microcystin-leucine-arginine (MC-LR) can enter into the brain and demonstrate neurotoxicity resulting in learning and memory deficits. While, there is still a lack of clear understanding of the related molecular mechanisms. In this study, we observed ß-amyloid (Aß) accumulation and tau hyperphosphorylation (p-tau) at sites of Ser396 and Thr205 in mouse hippocampus and cortex, Alzheimer's disease (AD) like changes, after chronic exposure to MC-LR at different concentrations (1, 7.5, 15 and 30 µg/L) for 180 days. The hallmarks of AD are characterized by senile plaques and neurofibrillary tangles (NFT), with associated loss of neurons, resulting in cognitive impairment and dementia. Similarly, the production of Aß and tau hyperphosphorylation was also detected in HT-22 cells treated with MC-LR. In addition, MC-LR promoted increased expressions of BACE1 and PS1, but reduced mRNA expressions of ADAM family members both in vivo and in vitro, promoting the Aß production. Moreover, we identified Akt/GSK-3ß signal pathway mediated the Aß and p-tau accumulation, bringing about Alzheimer's disease-like changes. Furthermore, microglial cells were activated in those mice exposed to MC-LR. Inflammatory cytokines were also found being activated to release in vitro. In conclusion, this study could provide a clue for MC-LR-induced neurotoxicity, which gave insights into the environmental risks of Alzheimer's disease.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Proteínas tau , Secretases da Proteína Precursora do Amiloide , Animais , Ácido Aspártico Endopeptidases , Quinase 3 da Glicogênio Sintase , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas tau/metabolismo
10.
Toxicology ; 459: 152860, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34280466

RESUMO

Di-n-butyl phthalate (DBP) is considered as a potential modifier of puberty. However, different results indicate that DBP plays an accelerated, delayed, or neutral role in the initiation of puberty. Furthermore, whether the effect of DBP on puberty will disrupt the function of reproductive system in the adults is still ambiguous. Therefore, we aimed to investigate the effect of maternal exposure to DBP on the onset of puberty in male offspring mice and the subsequent changes in the development of reproductive system. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. Compared with the control group, the 50 mg/kg/day DBP group accelerated puberty onset and testicular development were quite remarkable in male offspring mice during early puberty. Furthermore, in 22-day male offspring mice, 50 mg/kg/day DBP induced increased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in serum, and promoted the expression of steroidogenesis-related genes in the testes. Testicular Leydig cells (LCs) were isolated from the testes of 3-week-old mice and treated with 0 (control), 0.1, 1 mM monobutyl phthalate (MBP, the active metabolite of DBP) for 24 h. Consistent with the in vivo results, the expression of steroidogenesis-related genes and testosterone production were increased in LCs following exposure to 0.1 mM MBP. In adulthood, testes of the male offspring mice exposed to all doses of DBP exhibited adverse morphology compared with the control group. These results demonstrated that maternal exposure to 50 mg/kg/day DBP induced earlier puberty and precocious development of the testis, and eventually damaged the reproductive system in the later life.


Assuntos
Dibutilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento , Animais , Barreira Hematotesticular/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Exposição Materna , Camundongos , Camundongos Endogâmicos BALB C , Ácidos Ftálicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Espermatogênese/efeitos dos fármacos , Esteroides/biossíntese
11.
Ultrasound Med Biol ; 47(10): 2860-2868, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34315618

RESUMO

Ultrasound can be used to objectively diagnose and evaluate disease activity in patients with rheumatoid arthritis (RA). We aimed to determine the value of a new automated hand ultrasound (AHUS) scanning device and a simplified 3-joint ultrasound scoring system (US3) in detecting synovitis in RA. We compared AHUS and traditional ultrasound (US) scanning in detecting synovial hyperplasia (SH), joint effusion, bone erosion and power Doppler (PD) synovitis in 49 patients. In addition, we compared the value of US3 (in which 3 proximal interphalangeal [PIP] and/or metacarpophalangeal [MCP] joints with the highest scores for swelling and tenderness were evaluated) with the 22-joint ultrasound scoring system (US22) in 26 patients. Almost perfect κ coefficients (0.86-0.937) were obtained between AHUS and traditional US in detecting SH, joint effusion, bone erosion and PD synovitis (p < 0.001). The intra-class correlation coefficient (ICC) between AHUS and traditional US was 0.955-0.995. Of the US3 findings in AHUS, SH synovitis and PD synovitis were positively correlated with DAS28-CRP (adjusted R2 = 0.421, p < 0.0001; adjusted R2 = 0.365, p < 0.0001). US3 was highly correlated with US22 in detecting SH and PD synovitis (R = 0.792, p < 0.01; R = 0.948, p < 0.01). Compared with US22, a more significant correlation was identified between US3 scores and most clinical and laboratory values. In conclusion, AHUS performed comparably to traditional US in detecting synovitis in RA, and US3 was highly consistent with US22 in assessing synovitis and was positively correlated with RA disease activity.

12.
J Cell Mol Med ; 25(16): 7948-7960, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34155778

RESUMO

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans-Leuk1 epithelial cell co-culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking-induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans.

13.
Nat Commun ; 12(1): 2473, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931644

RESUMO

Programmable magnetic field-free manipulation of perpendicular magnetization switching is essential for the development of ultralow-power spintronic devices. However, the magnetization in a centrosymmetric single-layer ferromagnetic film cannot be switched directly by passing an electrical current in itself. Here, we demonstrate a repeatable bulk spin-orbit torque (SOT) switching of the perpendicularly magnetized CoPt alloy single-layer films by introducing a composition gradient in the thickness direction to break the inversion symmetry. Experimental results reveal that the bulk SOT-induced effective field on the domain walls leads to the domain walls motion and magnetization switching. Moreover, magnetic field-free perpendicular magnetization switching caused by SOT and its switching polarity (clockwise or counterclockwise) can be reversibly controlled in the IrMn/Co/Ru/CoPt heterojunctions based on the exchange bias and interlayer exchange coupling. This unique composition gradient approach accompanied with electrically controllable SOT magnetization switching provides a promising strategy to access energy-efficient control of memory and logic devices.

14.
J Hazard Mater ; 417: 126092, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015712

RESUMO

There is a growing concern regarding the toxic effects of nanoplastics (NPs) on aquatic and marine organism, while relatively few studies about their toxicity evaluation on mammals are conducted. In the present study, we observed accumulation of polystyrene NPs (PS NPs) in mice spleen, lung, kidney, small intestine, large intestine, testis, and brain after oral exposure to PS NPs (~100 nm, 10 mg/mL, 100 µL) for 28 days, and NPs were identified to induce cell apoptosis, inflammation, and structure disorder in these tissues. We also found that PS NPs could bring about hematological system injury and lipid metabolism disorder. Further in vitro studies identified that PS NPs could be absorbed by the intestinal epithelial Caco-2 cells by macropinocytosis and clathrin-mediated endocytosis, and induced disruption of tight junction between Caco-2 cells. Moreover, we found that it was easier for PS-NH2 and PS-COOH to enter into Caco-2 cells, which may be associated with observed stronger toxicity of PS-NH2 and PS-COOH NPs. In summary, this study demonstrated that NPs exposure brings about toxic effects to mice. This study could provide new insights regarding the distribution of NPs in humans, and helps us to evaluate the potential physiological risks of NPs to human beings.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Animais , Células CACO-2 , Humanos , Camundongos , Microplásticos , Nanopartículas/toxicidade , Poliestirenos/toxicidade
16.
Nat Commun ; 12(1): 2218, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850117

RESUMO

Revealing the atomistic mechanisms for the high-temperature mechanical behavior of materials is important for optimizing their properties for service at high-temperatures and their thermomechanical processing. However, due to materials microstructure's dynamic recovery and the absence of available in situ techniques, the high-temperature deformation behavior and atomistic mechanisms of materials are difficult to evaluate. Here, we report the development of a microelectromechanical systems-based thermomechanical testing apparatus that enables mechanical testing at temperatures reaching 1556 K inside a transmission electron microscope for in situ investigation with atomic-resolution. With this unique technique, we first uncovered that tungsten fractures at 973 K in a ductile manner via a strain-induced multi-step body-centered cubic (BCC)-to-face-centered cubic (FCC) transformation and dislocation activities within the strain-induced FCC phase. Both events reduce the stress concentration at the crack tip and retard crack propagation. Our research provides an approach for timely and atomic-resolved high-temperature mechanical investigation of materials at high-temperatures.

17.
Adv Sci (Weinh) ; 8(8): 2002051, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33898166

RESUMO

It remains a daunting task to quantify the configurational entropy of a material from atom-revolved electron microscopy images and correlate the results with the material's lattice thermal conductivity, which strides across statics, dynamics, and thermal transport of crystal lattice over orders of magnitudes in length and time. Here, a proof-of-principle study of atomic-scale visualization and quantification of configurational entropy in relation to thermal conductivity in single crystalline trigonal GeSb2Te4 (aka t-GeSb2Te4) with native atomic site disorder is reported. A concerted effort of large t-GeSb2Te4 single crystal growth, in-lab developed analysis procedure of atomic column intensity, the visualization and quantification of configurational entropy including corresponding modulation, and thermal transport measurements enable an entropic "bottom-up" perspective to the lattice thermal conductivity of t-GeSb2Te4. It is uncovered that the configurational entropy increases phonon scattering and reduces phonon mean free path as well as promotes anharmonicity, thereby giving rise to low lattice thermal conductivity and promising thermoelectric performance. The current study sheds lights on an atomic scale bottom-up configurational entropy design in diverse regimes of structural and functional materials research and applications.

18.
Nat Commun ; 12(1): 2023, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795654

RESUMO

Recently, there are significant progresses in the growth of organic-inorganic lead halide perovskite single crystals, however, due to their susceptible nucleation and growth mechanisms and solvent requirements, the efficient and generalized growth for these single crystals is still challenging. Here we report the work towards this target with a polymer-controlled nucleation process for the highly efficient growth of large-size high-quality simple ternary, mixed-cations and mixed-halide perovskite single crystals. Among them, the carrier lifetime of FAPbBr3 single crystals is largely improved to 10199 ns. Mixed MA/FAPbBr3 single crystals are synthesized. The crucial point in this process is suggested to be an appropriate coordinative interaction between polymer oxygen groups and Pb2+, greatly decreasing the nuclei concentrations by as much as 4 orders of magnitudes. This polymer-controlled route would help optimizing the solution-based OIHPs crystal growth and promoting applications of perovskite single crystals.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33845743

RESUMO

BACKGROUND: NONO-TFE3 translocation renal cell carcinoma (tRCC), one of RCCs associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCCs), involves an X chromosome inversion between NONO and TFE3 with the characteristics of endonuclear aggregation of NONO-TFE3 fusion protein. Nowadays, the oncogenic mechanisms of NONO-TFE3 fusion have not been fully elucidated. OBJECTIVE: This study aimed at investigating the mechanism of NONO-TFE3 fusion regulating HIF1A as well as the role of HIF-1α in the progression of NONO-TFE3 tRCC under hypoxia. METHODS: Immunohistochemistry and Western Blotting assays were performed to profile HIF-1α expression in renal clear cell carcinoma (ccRCC) or in Xp11.2 tRCC. Chromatin immunoprecipitation (ChIP), luciferase reporter assay and real-time quantitative PCR (RT-qPCR) were used to evaluate the regulation of HIF1A expression by NONO-TFE3 fusion. Then, flow cytometry analysis, tube formation assays and cell migration assays were used as well as glucose or lactic acid levels were measured to establish the impact of HIF-1α on the progression of NONO-TFE3 tRCC. Besides, the effect of HIF-1α inhibitor (PX-478) on UOK109 cells was analyzed. RESULTS: We found that HIF1A was targeting gene of NONO-TFE3 fusion. In UOK109 cells, which were isolated from NONO-TFE3 tRCC samples, NONO-TFE3 fusion promoted aerobic glycolysis and angiogenesis by up-regulating the expression of HIF-1α under hypoxia. Furthermore, inhibition of HIF-1α mediated by PX-478 suppressed the development of NONO-TFE3 tRCC under hypoxia. CONCLUSION: HIF-1α is a potential target for therapy of NONO-TFE3 tRCC under hypoxia.

20.
J Hematol Oncol ; 14(1): 46, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741027

RESUMO

BACKGROUND: NONO-TFE3 translocation renal cell carcinoma (NONO-TFE3 tRCC) is one subtype of RCCs associated with Xp11.2 translocation/TFE3 gene fusions RCC (Xp11.2 tRCCs). Long non-coding RNA (lncRNA) has attracted great attention in cancer research. The function and mechanisms of TRAF3IP2 antisense RNA 1 (TRAF3IP2-AS1), a natural antisense lncRNA, in NONO-TFE3 tRCC remain poorly understood. METHODS: FISH and qRT-PCR were undertaken to study the expression, localization and clinical significance of TRAF3IP2-AS1 in Xp11.2 tRCC tissues and cells. The functions of TRAF3IP2-AS1 in tRCC were investigated by proliferation analysis, EdU staining, colony and sphere formation assay, Transwell assay and apoptosis analysis. The regulatory mechanisms among TRAF3IP2-AS1, PARP1, PTEN and miR-200a-3p/153-3p/141-3p were investigated by luciferase assay, RNA immunoprecipitation, Western blot and immunohistochemistry. RESULTS: The expression of TRAF3IP2-AS1 was suppressed by NONO-TFE3 fusion in NONO-TFE3 tRCC tissues and cells. Overexpression of TRAF3IP2-AS1 inhibited the proliferation, migration and invasion of UOK109 cells which were derived from cancer tissue of patient with NONO-TFE3 tRCC. Mechanistic studies revealed that TRAF3IP2-AS1 accelerated the decay of PARP1 mRNA by direct binding and recruitment of N6-methyladenosie methyltransferase complex. Meanwhile, TRAF3IP2-AS1 competitively bound to miR-200a-3p/153-3p/141-3p and prevented those from decreasing the level of PTEN. CONCLUSIONS: TRAF3IP2-AS1 functions as a tumor suppressor in NONO-TFE3 tRCC progression and may serve as a novel target for NONO-TFE3 tRCC therapy. TRAF3IP2-AS1 expression has the potential to serve as a novel diagnostic and prognostic biomarker for NONO-TFE3 tRCC detection.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Proteínas de Ligação a DNA/genética , Neoplasias Renais/genética , PTEN Fosfo-Hidrolase/genética , Poli(ADP-Ribose) Polimerase-1/genética , Proteínas de Ligação a RNA/genética , RNA/genética , Adenosina/análogos & derivados , Adenosina/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , Proteínas de Fusão Oncogênica/genética , RNA Mensageiro/genética
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