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1.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118878, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33011193

RESUMO

Ovarian cancer is the deadliest gynaecologic malignancy, and the five-year survival rate of patients is less than 35% worldwide. Cancer stem cells (CSCs) are a population of cells with stem-like characteristics that are thought to cause chemoresistance and recurrence. TRIM29 is aberrantly expressed in various cancers and associated with cancer development and progression. Previous studies showed that the upregulation of TRIM29 expression in pancreatic cancer is related to stem-like characteristics. However, the role of TRIM29 in ovarian cancer is poorly understood. In this study, we found that TRIM29 expression was increased at the translational level in both the cisplatin-resistant ovarian cancer cells and clinical tissues. Increased TRIM29 expression was associated with a poor prognosis of patients with ovarian cancer. In addition, TRIM29 could enhance the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells. Recruitment of YTHDF1 to m6A-modified TRIM29 was involved in promoting TRIM29 translation in the cisplatin-resistant ovarian cancer cells. Knockdown of YTHDF1 suppressed the CSC-like characteristics of the cisplatin-resistant ovarian cancer cells, which could be rescued by ectopic expression of TRIM29. This study suggests TRIM29 may act as an oncogene to promote the CSC-like features of cisplatin-resistant ovarian cancer in an m6A-YTHDF1-dependent manner. Due to the roles of TRIM29 and YTHDF1 in the promotion of CSC-like features, they may become potential therapeutic targets to combat the recurrence of ovarian cancer.

2.
Cell Death Dis ; 11(9): 813, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994394

RESUMO

Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence, has a strong propensity for neck lymph node metastasis. Limited treatment options are available for patients with advanced or recurrent metastatic disease, resulting in a poor prognosis. Tripartite motif protein 29 (TRIM29) is dysregulated in various cancer and functions as oncogene or tumor suppressor in discrete cancers. In this study, we found that both TRIM29 and fibronectin 1 (FN1) were upregulated with positive correlation in PTC tissues. Neither overexpression nor downregulation of TRIM29 altered the proliferation of PTC cells significantly. Overexpression of TRIM29 significantly promotes, while knockdown of TRIM29 significantly decreases migration and invasion by regulating FN1 expression in PTC cells. In terms of mechanism, we found that TRIM29 altered the stability of FN1 mRNA via regulation of miR-873-5p expression. The current study also demonstrated that long non-coding RNA (LncRNA) CYTOR suppressed maturation of miR-873-5p via interaction with premiR-873, and TRIM29 decreased miR-873-5p via upregulation of CYTOR. This study suggests that involvement of TRIM29 in migration and invasion in PTC cells may reveal potential metastatic mechanism of PTC and represent a novel therapeutic target and strategy.

3.
Biochim Biophys Acta Mol Cell Res ; 1867(9): 118715, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32275930

RESUMO

Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for neck lymph node metastasis, which will increase the risk of local recurrence and decrease the survival in some high-risk groups. Hence, it is essential to set up a reliable biomarker to predict lymph node metastasis. BAG5 is a unique member of the BAG cochaperone family because it consists of more than one BAG domain, which acts as modulator of chaperone activity. In this study, we found that expression of BAG5 was significantly increased in PTC cells and tissues. Neither overexpression nor downregulation of BAG5 altered the proliferation of PTC cells. On the contrary, overexpression of BAG5 significantly promoted, while knockdown of BAG5 significantly decreased migration and invasion of PTC cells. Along with this, fibronectin 1 (FN1) was significantly increased and decreased in cells that overexpress or downregulate BAG5, respectively. Mechanistically, we found that BAG5 modulated FN1 expression at the translational level and promoted invasion via suppression of miR-144-3p, which targeted the 3' untranslational region (UTR) of FN1 transcript. This study suggests that BAG5 is an important regulator of migration and invasion in PTC cells and may represent a novel therapeutic target for intervening in PTC progression.

4.
Biochim Biophys Acta Mol Cell Res ; 1867(4): 118647, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31926942

RESUMO

Cisplatin-based chemotherapies have long been considered as a standard chemotherapy in ovarian cancer. However, cisplatin resistance restricts beneficial therapy for patients with ovarian cancer. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the post-translational modification of diverse proteins. In this work, we found that ISG15 was downregulated in cisplatin resistant tissues and cell lines of ovarian cancer. Functional studies demonstrated that overexpression of wild type (WT) ISG15, but not nonISGylatable (Mut) ISG15 increased cell responses to cisplatin in resistant ovarian cancer cells. Furthermore, we found that WT ISG15 decreased ABCC2 expression at the protein level. Importantly, overexpression of ABCC2 blocked sensitizing effect of ISG15 on cisplatin. In addition, we identified that hnRNPA2B1 was recruited to 5'UTR of ABCC2 mRNA and promoted its translation, which was blocked by ISG15. We further demonstrated that hnRNPA2B1 could be ISGylated, and ISGylation blocked its recruitment to ABCC2 mRNA, thereby suppressed translation of ABCC2. Altogether, our data support targeting ISG15 might be a potential therapeutic strategy for patients with cisplatin-resistant ovarian cancer.


Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Citocinas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neoplasias Ovarianas/genética , Biossíntese de Proteínas , Ubiquitinas/metabolismo , Regiões 5' não Traduzidas , Adulto , Idoso , Linhagem Celular Tumoral , Citocinas/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias Ovarianas/metabolismo , RNA Mensageiro/metabolismo , Ubiquitinas/genética
5.
J Cell Mol Med ; 24(1): 562-572, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31657880

RESUMO

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.

6.
J Cell Mol Med ; 23(8): 5006-5016, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31119886

RESUMO

BAG3 is constitutively expressed in multiple types of cancer cells and its high expression is associated with tumour progression and poor prognosis of PDAC. However, little is known about the role of BAG3 in the regulation of stromal microenvironment of PDAC. The current study demonstrated that beside PDAC tumour cells, BAG3 was also expressed in some activated stroma cells in PDAC tissue, as well as in activated PSCs. In addition, the current study demonstrated that BAG3 expression in PSCs was involved in maintenance of PSCs activation and promotion of PDACs invasion via releasing multiple cytokines. The current study demonstrated that BAG3-positive PSCs promoted invasion of PDACs via IL-8, MCP1, TGF-ß2 and IGFBP2 in a paracrine manner. Furthermore, BAG3 sustained PSCs activation through IL-6, TGF-ß2 and IGFBP2 in an autocrine manner. Thereby, the current study provides a new insight into the involvement of BAG3 in remodelling of stromal microenvironment favourable for malignant progression of PDAC, indicating that BAG3 might serve as a potential target for anti-fibrosis of PDAC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Células Estreladas do Pâncreas/metabolismo , Microambiente Tumoral/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
7.
Biochem Biophys Res Commun ; 513(4): 852-856, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31000199

RESUMO

Glucose limitation activates p53, which functions as an adaptive response to maintain cell survival. However, p53 is frequently deleted or mutated in a variety of tumors, while most cancer cells can acclimatize themselves to metabolically unfavorable surrounding, indicating that alternative mechanisms other than p53 transactivation underly adaptive response of cancer cells with p53 deletion or mutation to metabolically hostile environment. Sestrin 2 (SESN2) is a p53 downstream target, which plays a protective role against various stressful stimuli, such as genotoxic, energetic, and oxidative stress. In the current study, we demonstrated that SESN2 transcript was stabilized by glucose limitation at the posttranscriptional level irrespective of p53 status. Importantly, SESN2 also protected cells from metabolic stress triggered by glucose limitation in a p53-independent manner. Our data indicated that stabilization of SESN2 transcript might be an alternative adaptive response to metabolic stress other than p53 activation. Thereby, the current study highlights the significance of stabilization of SESN2 transcript in adaptation of cells with p53 deletion or mutation to metabolic stress.


Assuntos
Citoproteção , Proteínas Nucleares/metabolismo , Estresse Fisiológico , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Glucose/deficiência , Camundongos , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
8.
Cell Death Dis ; 10(4): 284, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-30910998

RESUMO

Bcl-2 associated athanogene 3 (BAG3) is an important molecule that maintains oncogenic features of cancer cells via diverse mechanisms. One of the important functions assigned to BAG3 is implicated in selective macroautophagy/autophagy, which attracts much attention recently. However, the mechanism underlying regulation of autophagy by BAG3 has not been well defined. Here, we describe that BAG3 enhances autophagy via promotion of glutamine consumption and glutaminolysis. Glutaminolysis initiates with deamination of glutamine by glutaminase (GLS), by which yields glutamate and ammonia in mitochondria. The current study demonstrates that BAG3 stabilizes GLS via prohibition its interaction with SIRT5, thereby hindering its desuccinylation at Lys158 and Lys164 sites. As an underlying molecular mechanism, we demonstrate that BAG3 interacts with GLS and decreases SIRT5 expression. The current study also demonstrates that occupation by succinyl at Lys158 and Lys164 sites prohibits its Lys48-linked ubiquitination, thereby preventing its subsequent proteasomal degradation. Collectively, the current study demonstrates that BAG3 enhances autophagy via stabilizing GLS and promoting glutaminolysis. For the first time, this study reports that succinylation competes with ubiquitination to regulate proteasomal GLS degradation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/genética , Estabilidade Enzimática/genética , Glutaminase/metabolismo , Glutamina/metabolismo , Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Amônia/metabolismo , Proteínas Reguladoras de Apoptose/genética , Glutaminase/genética , Células Hep G2 , Humanos , Células MCF-7 , Mitocôndrias/metabolismo , Neoplasias/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Sirtuínas/metabolismo , Transfecção , Ubiquitinação
9.
Biochim Biophys Acta Mol Cell Res ; 1866(5): 819-827, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30771383

RESUMO

BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes stemness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC). It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing Serine phosphorylation of Ago2 at position 387 (S387). Both BAG3 deletion and ISG15 knockdown suppressed stem cell-like phenotypes of PDAC cells, including clonogenicity, invasiveness and spheroid formation. In addition, ectopic ISG15 expression rescued the suppressive role of BAG3 deletion in cancer stem cell (CSC)-like phenotypes of PDAC cells, and this effect of ISG15 was independent of its ISGylation function. The current study implies that BAG3 and ISG15 may provide a therapeutic advantage for PDAC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Carcinoma Ductal Pancreático , Citocinas , Deleção de Genes , Proteínas de Neoplasias , Neoplasias Pancreáticas , Biossíntese de Proteínas , Ubiquitinas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Citocinas/biossíntese , Citocinas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ubiquitinas/biossíntese , Ubiquitinas/genética
10.
Cell Death Dis ; 9(9): 863, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30154469

RESUMO

Bcl-2 associated athanogene 3 (BAG3) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), and its high expression appears to be a poor prognostic factor for patients with PDAC. In this study, we show that BAG3 knockdown significantly decreases migration and invasion of PDACs via reduction of interleukine-8 (IL-8) production. BAG3 knockdown regulates IL-8 expression at the posttranscriptional levels via interplay between recruitment of RNA-binding protein HuR and miR-4312. HuR binds to the cis-elements located in the 3'-untranslational region (UTR) of the IL-8 transcript to stabilize it, whereas miR-4312-containing miRNA-induced silencing complex (miRISC) is recruited to the adjacent seed element to destabilize it. The binding of HuR prevents the recruitment of Argonaute (Ago2), overriding miR-4312-mediated translation inhibition of IL-8. BAG3 knockdown decreases cytoplasmic distribution of HuR via increasing its phosphorylation at Ser202, therefore compromising its recruitment while promoting recruitment of miR-4312 containing miRISC to IL-8 transcript. Furthermore, our data indicate that only phosphorylated Ago2 at Ser387 interacts with IL-8 transcript. BAG3 knockdown increases phosphorylation of Ago2 at Ser387, thereby further promoting loading of miR-4312 containing miRISC to IL-8 transcript. Taken together, we propose that BAG3 promotes invasion by stabilizing IL-8 transcript via HuR recruitment, and subsequently suppressing the loading of miR-4312 containing miRISC in PDACs. Our results reveal a novel pathway linking BAG3 expression to enhanced PDAC metastasis, thus making BAG3 a potential target for intervention in pancreatic cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Proteínas Reguladoras de Apoptose/genética , Carcinoma Ductal Pancreático/genética , Proteína Semelhante a ELAV 1/genética , Interleucina-8/genética , MicroRNAs/genética , RNA Mensageiro/genética , Regiões 3' não Traduzidas/genética , Proteínas Argonauta/genética , Linhagem Celular Tumoral , Humanos , Neoplasias Pancreáticas/genética
11.
Med Mycol ; 56(4): 458-468, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29420779

RESUMO

Iron-sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S. cerevisiae Atm1 was identified in C. neoformans, and its function was characterized. We constructed C. neoformans mutants lacking ATM1 and found that deletion of ATM1 affected mitochondrial functions. Furthermore, we observed diminished activity of the cytosolic ISC-containing protein Leu1 and the heme-containing protein catalase in the atm1 mutant. These results suggested that Atm1 is required for the biosynthesis of ISCs in the cytoplasm as well as heme metabolism in C. neoformans. In addition, the atm1 mutants were avirulent in a murine model of cryptococcosis. Overall, our results demonstrated that Atm1 plays a critical role in iron metabolism and virulence for C. neoformans.


Assuntos
Cryptococcus neoformans/genética , Cryptococcus neoformans/patogenicidade , Proteínas Fúngicas , Ferro/metabolismo , Mitocôndrias/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Criptococose/metabolismo , Criptococose/patologia , Cryptococcus neoformans/metabolismo , Cryptococcus neoformans/ultraestrutura , Modelos Animais de Doenças , Feminino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Humanos , Proteínas com Ferro-Enxofre/biossíntese , Proteínas com Ferro-Enxofre/genética , Leucina/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/genética , Saccharomyces cerevisiae/genética , Deleção de Sequência , Superóxido Dismutase/genética , Virulência/genética
12.
J Cell Biol ; 216(12): 4091-4105, 2017 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-29114069

RESUMO

Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Proteínas Reguladoras de Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Hexoquinase/genética , Neoplasias Pancreáticas/genética , Proteínas de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/genética , Endonucleases/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Edição de Genes , Glucose/metabolismo , Glicólise/genética , Hexoquinase/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Cultura Primária de Células , RNA Guia/genética , RNA Guia/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
13.
Cell Death Dis ; 8(7): e2933, 2017 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-28703799

RESUMO

BAG3 is an evolutionarily conserved co-chaperone expressed at high levels and has a prosurvival role in many tumor types. The current study reported that BAG3 was induced under specific floating culture conditions that enrich breast cancer stem cell (BCSC)-like cells in spheres. Ectopic BAG3 overexpression increased CD44+/CD24- CSC subpopulations, first-generation and second-generation mammosphere formation, indicating that BAG3 promotes CSC self-renewal and maintenance in breast cancer. We further demonstrated that mechanically, BAG3 upregulated CXCR4 expression at the post-transcriptional level. Further studies showed that BAG3 interacted with CXCR4 mRNA and promoted its expression via its coding and 3'-untranslational regions. BAG3 was also found to be positively correlated with CXCR4 expression and unfavorable prognosis in patients with breast cancer. Taken together, our data demonstrate that BAG3 promotes BCSC-like phenotype through CXCR4 via interaction with its transcript. Therefore, this study establishes BAG3 as a potential adverse prognostic factor and a therapeutic target of breast cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/patologia , Receptores CXCR4/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Autorrenovação Celular , Feminino , Meia-Vida , Compostos Heterocíclicos/farmacologia , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Receptores CXCR4/genética , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Regulação para Cima/efeitos dos fármacos
14.
Sci Rep ; 7(1): 4841, 2017 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-28687793

RESUMO

A flexible riverbed protection called tetrahedron framed permeable weirs (TFPW) is proposed to protect riverbeds in mountainous areas from scouring. Under clear water conditions, a series of laboratory flume experiments were performed to study the effects of TFPW with different layout types on the stability of riverbeds. The objectives of this paper were to advance understanding of the role that TFPW play in the erosion process of river beds and to optimize the TFPW design for reducing velocity, promoting sediment deposition and good structural stability. Data on velocity distribution and variation, equilibrium bathymetry, flow resistance, bed form characteristics and structural stability were collected and analyzed. The results indicate that (1) with good structural stability, all the TFPW with different layout types had significant effects on the stabilization of the riverbed by reducing velocity, raising the water level, increasing the roughness coefficient, protecting the riverbed from degradation and promoting deposition; and (2) the random Double TFPW with large rates of deceleration, large deposition ranges, and good structural stability, and the paved Single TFPW with small rates of deceleration but large deposition ranges and perfect structural stability, were suitable and optimal for riverbed protection in a clear water channel.

16.
J Agric Food Chem ; 63(14): 3627-33, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25822065

RESUMO

In fields of transgenic Bt rice, frogs are exposed to Bt proteins through consumption of both target and nontarget insects. In the present study, we assessed the risk posed by transgenic rice expressing a Cry1Ab/1Ac fusion protein (Huahui 1, HH1) on the development of Xenopus laevis. For 90 days, froglets were fed a diet with 30% HH1 rice, 30% parental rice (Minghui 63, MH63), or no rice as a control. Body weight and length were measured every 15 days. After sacrificing the froglets, we performed a range of biological, clinical, and pathological assessments. No significant differences were found in body weight (on day 90: 27.7 ± 2.17, 27.4 ± 2.40, and 27.9 ± 1.67 g for HH1, MH63, and control, respectively), body length (on day 90: 60.2 ± 1.55, 59.3 ± 2.33, and 59.7 ± 1.64 mm for HH1, MH63, and control, respectively), animal behavior, organ weight, liver and kidney function, or the microstructure of some tissues between the froglets fed on the HH1-containing diet and those fed on the MH63-containing or control diets. This indicates that frog development was not adversely affected by dietary intake of Cry1Ab/1Ac protein.


Assuntos
Proteínas de Bactérias/genética , Endotoxinas/genética , Alimentos Geneticamente Modificados , Proteínas Hemolisinas/genética , Oryza/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Xenopus laevis/crescimento & desenvolvimento , Xenopus laevis/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Bioensaio , Endotoxinas/metabolismo , Inocuidade dos Alimentos , Proteínas Hemolisinas/metabolismo , Modelos Animais , Oryza/genética , Plantas Geneticamente Modificadas/genética
17.
Ecotoxicology ; 23(9): 1619-28, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25129148

RESUMO

As genetic engineering in plants is increasingly used to control agricultural pests, it is important to determine whether such transgenic plants adversely affect non-target organisms within and around cultivated fields. The cry1Ab/1Ac fusion gene from Bacillus thuringiensis (Bt) has insecticidal activity and has been introduced into rice line Minghui 63 (MH63). We evaluated the effect of transgenic cry1Ab/1Ac rice (Huahui 1, HH1) on paddy frogs by comparing HH1 and MH63 rice paddies with and without pesticide treatment. The density of tadpoles in rice fields was surveyed at regular intervals, and Cry1Ab/1Ac protein levels were determined in tissues of tadpoles and froglets collected from the paddy fields. In addition, Rana nigromaculata froglets were raised in purse nets placed within these experimental plots. The survival, body weight, feeding habits, and histological characteristics of the digestive tract of these froglets were analyzed. We found that the tadpole density was significantly decreased immediately after pesticide application, and the weight of R. nigromaculata froglets of pesticide groups was significantly reduced compared with no pesticide treatment, but we found no differences between Bt and non-Bt rice groups. Moreover, no Cry1Ab/1Ac protein was detected in tissue samples collected from 192 tadpoles and froglets representing all four experimental groups. In addition, R. nigromaculata froglets raised in purse seines fed primarily on stem borer and non-target insects, and showed no obvious abnormality in the microstructure of their digestive tracts. Based on these results, we conclude that cultivation of transgenic cry1Ab/1Ac rice does not adversely affect paddy frogs.


Assuntos
Anuros , Proteínas de Bactérias/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Oryza/crescimento & desenvolvimento , Praguicidas/toxicidade , Animais , Peso Corporal , Monitoramento Ambiental , Larva/efeitos dos fármacos , Oryza/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Densidade Demográfica
18.
Gene ; 547(2): 280-7, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24976171

RESUMO

Cofilins (CFL), including CFL1 and CFL2, are members of the family of actin-binding proteins in eukaryote. CFL2 is predominantly expressed in mammalian skeletal muscle and heart and is important to muscle fiber formation and muscular regeneration. To study transcriptional regulation of porcine CFL2, a 2.5 kb upstream sequence starting from the major CFL2 transcriptional start site was cloned by genome walking. Twelve DNA fragments of the 5' flank region of the porcine CFL2 gene were further isolated from porcine genomic DNA via PCR and inserted into the luciferase reporter vector pGL4.10 to make 12 CFL2 reporter constructs. All reporter vectors were transfected into C2C12, NIH3T3, or Hela cells and their relative luciferase activity measured after 48 h, respectively. Bioinformatics analysis suggested that there were two TATA-boxes at the -508 bp and -453 bp, as well as a GC-box and a CAAT-box in this sequence. Additional transcription factor binding sites including SP1, AP1, AP2, and GATA-1 sites were also predicted. The transcriptional activity of pGL4.10-1554 (1502 bp to +51 bp) was the strongest, and the promoter's active region was mapped to a region from -1502 bp to -1317 bp. Our data provide a foundation for future studies into transcriptional regulation of CFL2.


Assuntos
Cofilina 2/genética , Regiões Promotoras Genéticas , Animais , Sequência de Bases , Clonagem Molecular , Cofilina 2/metabolismo , Células HeLa , Humanos , Camundongos , Dados de Sequência Molecular , Células NIH 3T3 , Suínos , Transcrição Genética
19.
Gene ; 545(1): 56-60, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24809963

RESUMO

Lactose intolerance in northern Europeans is strongly associated with a single-nucleotide polymorphism (SNP) located 14 kb upstream of the human lactase gene: -13,910 C/T. We examined whether SNPs in the 5' flanking region of the pig lactase gene are similar to those in the human gene and whether these polymorphisms play a functional role in regulating pig lactase gene expression. The 5' flanking region of the lactase gene from several different breeds of pigs was cloned and analyzed for gene regulatory activity of a luciferase reporter gene. One SNP was found in the enhancer region (-797 G/A) and two were found in the promoter region (-308G/C and -301 A/G). The promoter C-308,G-301(Pro-CG) strongly promotes the expression of the lactase gene, but the promoter G-308,A-301(Pro-GA) does not. The enhancer A-797(Enh-A) genotype for Pro-GA can significantly enhance promoter activity, but has an inhibitory effect on Pro-CG. The Enhancer G-797(Enh-G) has a significant inhibitory effect on both promoters. In conclusion, the order of effectiveness on the pig lactase gene is Enh-A+Pro-GA>Enh-A/G+Pro-CG>Enh-G+Pro-GA.


Assuntos
Elementos Facilitadores Genéticos , Lactase/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Sus scrofa/genética , Animais , Regulação da Expressão Gênica , Lactase/metabolismo
20.
Photodermatol Photoimmunol Photomed ; 29(5): 233-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24001378

RESUMO

BACKGROUND: Acne conglobata is hardly curable and easily leads to scar formation after treatment using traditional methods. AIM: To develop a novel way to treat acne conglobata. METHODS: Seventy-five patients with facial acne conglobata were included in this clinical study and divided into either a treatment group (n = 35) to receive photodynamic therapy (PDT) with topical 5% 5-aminolevulinic acid and red light once every 10 days for a month or a control group (n = 40) to receive a Chinese herbal medicine mask plus red light once per week for the same duration. Patients in both groups were given oral viaminate capsules, doxycycline, zinc gluconate, and topical metronidazole. Efficacy was evaluated with respect to symptom score, cure rate, and response rate up to 2 weeks following the final treatment, and time points for assessment included baseline (D0 ), the visit before each treatment (D10 and D20 for the treatment group, and D7 , D14 , and D21 for the control group), and 2 weeks after treatment (D34 for the treatment group and D35 for the control group). Safety was assessed by recording adverse effects. RESULTS: Treatment with PDT significantly improved acne lesions and reduced scar formation. The treatment group had a significantly lower symptom score, a higher cure rate, and response rate than the control group. No systemic side effects occurred. CONCLUSION: The treatment of acne conglobata with PDT is associated with a high cure rate, short treatment period, few side effects, and reduced scar formation. To the best of our knowledge, this is the first report on the treatment of acne conglobata with PDT.


Assuntos
Acne Queloide/tratamento farmacológico , Ácido Aminolevulínico/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Acne Queloide/patologia , Adulto , Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Face/patologia , Feminino , Gluconatos/administração & dosagem , Humanos , Masculino , Metronidazol/administração & dosagem , Estudos Prospectivos , Fatores de Tempo
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