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1.
Cell Death Dis ; 12(4): 347, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795650

RESUMO

Papillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial-mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33653254

RESUMO

BACKGROUND: Hepatitis B virus X protein (HBx) is an indispensable progression factor in hepatocellular carcinoma (HCC). CCL15 could be a peculiar proteomic biomarker of HCC with tumorigenesis and tumor invasion. OBJECTIVE: The aim of study was to explore the relationship between HBx and CCL15 expression in HCC. METHODS: HBV-positive HCC pathological tissue samples and corresponding adjacent non-tumor liver tissues were clearly collected. The expression of HBx and CCL15 was analyzed by immunohistochemistry, real-time polymerase chain reaction (PCR) and western blot analysis in tissues or in vitro. RESULTS: The levels of CCL15 mRNA and protein expression in HCC samples were observably higher than the ones of adjacent non-tumor liver tissues. The CCL15 was significantly associated with the expression of HBx in HBV-positive HCC samples. The up-regulation of HBx induced CCL15 expression in vitro. The high expression score of CCL15 was significant associated with the poor prognosis of HCC patients. CONCLUSIONS: The CCL15 expression was observably associated with HBx in HCC patients. The CCL15 may be considered as a indicator in clinical managment of HBV-associated HCC.

3.
ACS Appl Mater Interfaces ; 13(5): 6043-6052, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33525876

RESUMO

DNA methylation is a kind of a crucial epigenetic marker orchestrating gene expression, molecular function, and cellular phenotype. However, manipulating the methylation status of specific genes remains challenging. Here, a clustered regularly interspaced palindromic repeats-Cas9-based near-infrared upconversion-activated DNA methylation editing system (CNAMS) was designed for the optogenetic editing of DNA methylation. The fusion proteins of photosensitive CRY2PHR, the catalytic domain of DNMT3A or TET1, and the fusion proteins for CIBN and catalytically inactive Cas9 (dCas9) were engineered. The CNAMS could control DNA methylation editing in response to blue light, thus allowing methylation editing in a spatiotemporal manner. Furthermore, after combination with upconversion nanoparticles, the spectral sensitivity of DNA methylation editing was extended from the blue light to near-infrared (NIR) light, providing the possibility for remote DNA methylation editing. These results demonstrated a meaningful step forward toward realizing the specific editing of DNA methylation, suggesting the wide utility of our CNAMS for functional studies on epigenetic regulation and potential therapeutic strategies for related diseases.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Edição de Genes , Técnicas Genéticas , Raios Infravermelhos , Neoplasias da Glândula Tireoide/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/genética , Proteína 9 Associada à CRISPR/metabolismo , Sobrevivência Celular , Células Cultivadas , Metilação de DNA/genética , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Experimentais/genética , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Tamanho da Partícula , Propriedades de Superfície , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia
4.
PeerJ ; 8: e9675, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194342

RESUMO

Objective: To explore the relationship between body mass index (BMI) and clinicopathological characteristics in patients with papillary thyroid carcinoma (PTC). Methods: The clinical data of 1,579 patients with PTC, admitted to our hospital from May 2016 to March 2017, were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight recombination (BMI < 18.5 kg/m), normal body recombination (18.5 ≤ BMI < 24.0 kg/m2), overweight recombination (24.0 ≤ BMI < 28.0 kg/m2) and obesity group (BMI ≥ 28.0 kg/m2). The clinicopathological characteristics of PTC in patients with different BMIs group were compared. Results: In our study, the risk for extrathyroidal extension (ETE), advanced T stage (T III/IV), and advanced tumor-node-metastasis stage (TNM III/IV) in the overweight group were higher, with OR (odds ratio) = 1.99(1.41-2.81), OR = 2.01(1.43-2.84), OR = 2.94(1.42-6.07), respectively, relative to the normal weight group. The risk for ETE and T III/IV stage in the obese group were higher, with OR = 1.82(1.23-2.71) and OR = 1.82(1.23-2.70), respectively, relative to the normal weight group. Conclusion: BMI is associated with the invasiveness of PTC. There is a higher risk for ETE and TNM III/IV stage among patients with PTC in the overweight group and for ETE among patients with PTC in the obese group.

5.
Cell Death Dis ; 11(10): 839, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037185

RESUMO

Polyamine biosynthesis is an essential metabolic pathway for cell growth and differentiation in non-small-cell lung cancer (NSCLC). Fragile-site associated tumour suppressor (FATS) is a novel gene involved in cancer. The results of our previous study showed that FATS-mediated polyubiquitination of p53 promotes the activation of p53 in response to DNA damage; however, little is known about the role of FATS in metabolic reprogramming in NSCLC. In the present study, FATS was observed to be significantly downregulated in NSCLC tissues compared with paired adjacent normal tissues and was associated with the survival of NSCLC patients. We further showed that the presence of the tumour suppressor FATS in NSCLC cells led to apoptosis by inducing pro-death autophagy. In addition, FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, which was partially dependent on oestrogen receptor (ER). Furthermore, FATS was observed to bind to ERß and translocate to the cytosol, leading to ODC degradation. The findings of our study demonstrate that FATS plays important roles in polyamine metabolism in NSCLC and provides a new perspective for NSCLC progression.

6.
Front Oncol ; 10: 217, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219060

RESUMO

Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC.

7.
Integr Environ Assess Manag ; 16(3): 392-399, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31944533

RESUMO

Adsorption of polycyclic aromatic hydrocarbons (PAHs) on root surfaces has essential impacts on PAH phytoremediation. An Fe plaque is commonly formed on the root surface of aquatic plants. Therefore, it is worth investigating the impact of the Fe plaque on PAH adsorption on rice root surfaces. Using Bayesian linear water-methanol cosolvent models, we estimated accurate water-biosorbent partition coefficient values for phenanthrene, pyrene, and benzo[a]pyrene between water and rice root biosorbent fractions, including rice root materials with Fe plaque, removed Fe plaque, and removed Fe plaque and lipids. Our results showed that Fe plaque inhibited the adsorption of PAHs on rice root surface; the inhibition impacts increased with hydrophobicity of PAHs. This result highlights the need for considering the impact of Fe plaque on PAH adsorption during phytoremediation. Integr Environ Assess Manag 2020;16:392-399. © 2020 SETAC.


Assuntos
Ferro , Oryza , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Adsorção , Teorema de Bayes
8.
Int J Clin Oncol ; 25(1): 59-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31414270

RESUMO

BACKGROUND: The aim of this study was to evaluate the prognostic veracity for disease-specific survival (DSS) of the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in a Chinese population of patients with differentiated thyroid carcinoma (DTC) and to evaluate the impact of N1b redefinition and reclassification on prediction of survival. METHODS: A total of 569 DTC patients who underwent thyroid surgery in two Chinese hospitals were included in analysis to assess the predictive accuracy and N1b changes of TNM-8. Data from the Surveillance, Epidemiology and End Results (SEER) program were applied to validate the findings on N1b changes of TNM-8. Unadjusted DSS was calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the association of stage and lymph node metastasis (LNM) status with survival. The proportion of variation explained (PVE), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were evaluated to compare model performance. RESULTS: When TNM-8 was applied, 39.7% of patients were downstaged relative to TMN-7. In comparison of TNM-7 and TMN-8, the PVE was 18.68% and 22.33%, the AIC was 704.22 and 680.50, and the BIC was 702.98 and 679.24, respectively. In 569 Chinese patients with DTC, levels I-V LNM was significantly related to poorer DSS compared with N0 and level VI LNM. Among patients aged ≥ 55 years, those with levels I-V and VII LNM had significantly worse DSS than those with N0 and Level VI LNM. In the SEER dataset, patients with levels I-V and VII LNM had significantly worse DSS compared with those with N0 and Level VI LNM, especially in older patients (age ≥ 55 years). CONCLUSIONS: TNM-8 staged a significant number of Chinese patients into lower stages and improved the accuracy of predicting DSS compared with TNM-7. However, changes in lateral LNM definition and classification of TNM-8 have a significant prognostic implication for patients with DTC, especially older patients (≥ 55 years). Our data suggest that a modified TNM staging system would be more useful for predicting mortality and determining a proper treatment strategy in patients with DTC.


Assuntos
Adenocarcinoma Papilar/patologia , Estadiamento de Neoplasias/normas , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Papilar/mortalidade , Adenocarcinoma Papilar/cirurgia , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Hospitais , Humanos , Linfonodos/patologia , Masculino , Oncologia/organização & administração , Oncologia/normas , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia
9.
Cancer Med ; 8(18): 7644-7649, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31691509

RESUMO

At present, hypoechogenicity, as one of the clinically relevant features associated with suspicion of malignant thyroid disease, is affected by the variability of modules and the experience of sonographers, thus leading to unsatisfying results. We propose the ultrasound gray scale ratio (UGSR) to obtain an objective, numerical estimate of the echogenicity degree in different-sized thyroid nodules, and we then evaluate its diagnostic efficacy in differentiating benign and malignant thyroid lesions. In total, 553 ultrasound images of thyroid nodules from one kind of ultrasonographic scanner were analyzed, among which 281 were papillary thyroid carcinomas (PTCs) and 272 were nodular goiters (NGs). The UGSR of the PTCs, NGs, and surrounding normal thyroid tissue was measured by image analysis software. The best cut-off value for distinguishing various sizes of PTCs and NGs was determined by receiver operating characteristic (ROC) curve analysis. As the UGSR increased, the sensitivity of the diagnosing PTCs decreased, and the specificity increased. When the maximum Jordan index was 0.611, the best cut-off value was 0.692, and the corresponding sensitivity and specificity of diagnosing PTCs were 87.9% and 73.2%, respectively. For the analysis of subgroups of different tumor sizes, as the size of thyroid nodules increased from 0.3 to 2 cm, the sensitivity of the diagnosis of PTCs decreased from 97.5% to 58.8%, and the specificity increased from 72.4% to 90.9%. These results strongly suggest that the UGSR is an appropriate objective, numerical method for estimating the echogenicity degree and has various diagnostic efficacies in different-sized thyroid nodules. Thus, the UGSR can be used as an additional ultrasound parameter in the diagnosis of different-sized PTCs and NGs.


Assuntos
Processamento de Imagem Assistida por Computador , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia , Diagnóstico Diferencial , Humanos , Processamento de Imagem Assistida por Computador/métodos , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Carga Tumoral , Ultrassonografia/métodos
10.
Onco Targets Ther ; 12: 6937-6945, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695409

RESUMO

Background: Anaplastic thyroid carcinoma (ATC) is the most aggressive cancer in humans with no optimal treatment strategy available. The molecular mechanisms of ATC remain unclear. The aim of this study was to investigate the prognostic value and role of BRMS1 in the progression of ATC. Methods: BRMS1 expression was examined in thyroid cell lines using Western blot analysis. Immunohistochemistry was also performed to assess BRMS1 expression in ATC and papillary thyroid cancer (PTC) tissue. Cell proliferation assays, colony formation analysis, cell migration assays, cell apoptosis analysis, and animal studies were used to examine the effects of BRMS1 expression on ATC progression. Results: The expression of BRMS1 was significantly lower in ATC than in PTC and was associated with poor prognosis in ATC patients. Downregulation of BRMS1 expression promoted the proliferation and migration of 8505C cells and decreased their expression of CX43. Over-expressed BRMS1 promoted the apoptosis and impaired the proliferation and migration of CAL-62 cells via upregulated CX43. In vivo, BRMS1 significantly promoted apoptosis and impaired cell proliferation. Conclusion: Taken together, these findings demonstrate that decreased expression of BRMS1 is a poor prognostic biomarker in ATC patients. BRMS1 significantly promoted apoptosis and impaired cell proliferation via CX43 and P53. Loss of BRMS1 expression is therefore, one of the key pathomechanisms in ATC.

11.
Cancer Manag Res ; 11: 3765-3777, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118795

RESUMO

Objective: Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major producer of mitochondrial NADPH. IDH2-related research has focused on its mutation mechanism and its clinical significance, but the role of wild-type IDH2 in carcinoma remains controversial. Altered IDH2 levels have been identified in several types of carcinomas. However, the significance and expression of IDH2 in thyroid cancer remains unknown. Methods: We examined the expression of IDH2 in thyroid cancer and adjacent normal tissues using quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining analyses, and western blot analysis with frozen tissues. The relationship between IDH2 and the clinicopathological features of thyroid cancer was analyzed by IHC. Subsequently, we investigated the function of wild-type IDH2 in thyroid cancer cells in vitro. Results: We found that the mRNA expression and protein levels of IDH2 were higher in tumor than in adjacent tissues, when evaluated by qRT-PCR, western blot, and IHC analyses. Tumor size, T stage, lymph node metastasis, and TNM stage showed significant differences between the IDH2 high expression and low expression groups. Multiple logistic regression analyses indicated that tumor size and IDH2 expression were significantly correlated with the occurrence of neck LNM. Furthermore, CCK8 levels, colony formation, and invasive cell number were decreased in the sh-IDH2 groups. The upregulation of IDH2 in thyroid cancer cells showed opposite effects. Conclusion: Our results indicated that IDH2 may play an important role in the development of thyroid cancer. IDH2 can be used as a potential biomarker for diagnosis and prognosis and may be a potential therapeutic target for thyroid cancer.

12.
Endocr Relat Cancer ; 26(1): 141-151, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30400007

RESUMO

Anaplastic thyroid cancer (ATC) is an aggressive cancer with poor clinical prognosis. However, mechanisms driving ATC aggressiveness is not well known. Components of the DNA damage response (DDR) are frequently found mutated or aberrantly expressed in ATC. The goal of this study is to establish the functional link between histone acetyltransferase lysine (K) acetyltransferase 5 (KAT5, a critical DDR protein) and ATC invasiveness using clinical, in vitro and in vivo models. We analyzed the expression of KAT5 by immunohistochemistry and assessed its relationship with metastasis and overall survival in 82 ATC patients. Using cellular models, we established functional connection of KAT5 expression and C-MYC stabilization. We then studied the impact of genetically modified KAT5 expression on ATC metastasis in nude mice. In clinical samples, there is a strong correlation of KAT5 expression with ATC metastasis (P = 0.0009) and overall survival (P = 0.0017). At the cellular level, upregulation of KAT5 significantly promotes thyroid cancer cell proliferation and invasion. We also find that KAT5 enhances the C-MYC protein level by inhibiting ubiquitin-mediated degradation. Further evidence reveals that KAT5 acetylates and stabilizes C-MYC. Finally, we prove that altered KAT5 expression influences ATC lung metastases in vivo. KAT5 promotes ATC invasion and metastases through stabilization of C-MYC, demonstrating it as a new biomarker and therapeutic target for ATC.


Assuntos
Lisina Acetiltransferase 5/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Acetilação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/secundário , Lisina Acetiltransferase 5/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/mortalidade , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
13.
J Cancer ; 9(18): 3257-3262, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271484

RESUMO

Understanding the functional significance of the essential elements in maintaining genomic stability provides insights into the process of tumor initiation and progression, and predicts therapeutic responses. One such element that has recently attracted significant attention is the Speckle-Type Poz Protein (SPOP), an E3 ubiquitin ligase adaptor protein. SPOP is frequently mutated or has altered expression in various cancers, including prostate, renal and endometrial. SPOP is involved in the regulation of proteasome-mediated degradation of several oncoproteins. Moreover, recent data also indicate SPOP's direct involvement in the DNA damage response. SPOP mutants induce alternations in the DNA damage repair pathway by promoting the error-prone Non-homologous end joining (NHEJ) pathway. SPOP has been linked with significant functions in cellular signaling pathways and cancer suppression. This mini-review will discuss recent findings regarding SPOP's role in genomic stability in the pathological setting.

14.
Environ Res ; 111(3): 356-61, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21316043

RESUMO

Our aim was to investigate rhizosphere effects on the chemical behavior of Cd. This was done in a glasshouse experiment, where two rice cultivars (Zhenong54 and Sixizhan) were grown in soil spiked with cadmium (Cd) at two levels, 3.9 ± 0.5 and 8.3 ± 0.5 mg kg(-1) soil, placed in a rhizobox until ripening stage. Chemical forms of cadmium near the root surface were then assessed using a sequential extraction procedure (SEP). There were significant differences in Cd species, especially exchangeable Cd (EXC-Cd) between the two rice cultivars as affected by rice roots. The lowest EXC-Cd with Zhenong54 appeared in the near-rhizosphere area with little difference between tillering stage and ripening stage while Sixizhan had its lowest EXC-Cd concentration in the root compartment. Both cultivars had slight changes in the Fe/Mn oxide-bound fraction of Cd (FMO-Cd) at the grain ripening stage while the control treatments without plants had a significant increase in FMO-Cd at the same time, indicating a transformation from a less bioavailable form (FMO-Cd) to more bioavailable forms (EXC-Cd). Soil microbial biomass in the vicinity of the root surface had opposite trends to some extent with EXC-Cd, partly because of the root-induced changes to bioavailable Cd. Unlike Zhenong54, Sixizhan had a higher Cd concentration in the root, but only a small proportion of Cd translocated from the root to grain.


Assuntos
Cádmio/química , Oryza/metabolismo , Rizosfera , Poluentes do Solo/química , Cádmio/metabolismo , Genótipo , Oryza/genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Poluentes do Solo/metabolismo
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