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1.
Environ Toxicol ; 38(11): 2705-2716, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37471645

RESUMO

Curcumin shows an anti-cancer role in many kinds of tumors. However, the mechanism of its anti-tumor function in esophageal squamous cell carcinoma (ESCC) remains largely unknown. Herein, we explored the therapeutic potential of curcumin for esophageal cancer. Curcumin could time- and dose-dependently inhibit ESCC cells activity. Additionally, ESCC cells exposed to 20 µM of curcumin exhibited significantly decreased proliferative and invasive capacities, as well as enhanced cell apoptosis. ESCC tissues and cells exhibited significantly increased circNRIP1 expression when compared to their counterparts. circNRIP1 knockdown markedly impaired cell proliferation, clone formation, cell migration and invasion but promoted apoptosis. Exposure to 10-20 µM of curcumin inhibited circNRIP1 expression, however, overexpression of circNRIP1 could significantly restored the biological characteristics that were inhibited by curcumin exposure in vivo and in vitro. circNRIP1 promoted the malignancy of ESCC by combining miR-532-3p, and downstream AKT3. Curcumin inhibited AKT phosphorylation by up-regulating miR-532-3p expression, thereby inhibiting the activation of the AKT pathway. In summary, curcumin is a potent inhibitor of ESCC growth, which can be achieved through the regulation of the circNRIP1/miR-532-3p/AKT pathway. This research may provide new mechanisms for curcumin to inhibit the malignant development of ESCC.


Assuntos
Curcumina , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Curcumina/farmacologia , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica
2.
Environ Toxicol ; 38(10): 2462-2475, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37449723

RESUMO

Circ_LRP6 is participated in the occurrence and development of numerous tumors. Nevertheless, its roles and mechanism in osteosarcoma (OS) is unknown. This study aims to illustrate this point. With the use of qRT-PCR, the level of circ_LRP6, miR-122-5p, miR-204-5p and HMGB1 was identified. To observe cell proliferation, migration and invasion, we adopted CCK-8 and Transwell assays in the present study. Besides, to prove the existing interaction, bioinformatics analysis and dual luciferase reporting assays were employed. The influence of circ_LRP6 on osteosarcoma in vivo was evaluated by subcutaneous tumor formation model in nude mice. In osteosarcoma tissues, circ_LRP6 and HMGB1 are strongly denoted, whereas miR-122-5p and miR-204-5p are under-expressed. Circ_LRP6 knockdown could significantly hinder the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 hindered the proliferation of osteosarcoma in vivo. Bioinformatics predicted that miR-122-5p and miR-204-5p functioned as direct targets of circ_LRP6, and HMGB1 were possible target genes of miR-122-5p and miR-204-5p. The findings indicated that the low level of miR-122-5p and miR-204-5p and the overexpression of HMGB1 could partially restore and reduce the inhibitory impact of circ_LRP6 on the proliferation, migration and invasion of osteosarcoma cells. Circ_LRP6 affects osteosarcoma progression via the miR-122-5p/miR-204-5p/HMGB1 axis, and is shown to be a molecular biomarker.


Assuntos
Neoplasias Ósseas , Proteína HMGB1 , MicroRNAs , Osteossarcoma , Animais , Camundongos , Proteína HMGB1/genética , Camundongos Nus , Osteossarcoma/genética , Proliferação de Células/genética , Neoplasias Ósseas/genética , MicroRNAs/genética , Linhagem Celular Tumoral
3.
J Cell Physiol ; 234(5): 7266-7278, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30362591

RESUMO

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.


Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/enzimologia , Quinases Associadas a rho/metabolismo , Adulto , Sítios de Ligação , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Quinases Associadas a rho/genética
4.
J Cell Physiol ; 234(6): 8998-9007, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30317613

RESUMO

A growing amount of evidence has shown that long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS). However, little knowledge is available about the functional roles and molecular mechanisms of lncRNA Alu-mediated p21 transcriptional regulator (APTR) in OS. Herein, APTR expression was demonstrated to be significantly upregulated in OS tumor tissues and four OS cell lines (including MG63, 143B, Saos-2, and HOS) compared with the adjacent tissues and human osteoblast cell line hFOB1.19, respectively. We confirmed miR-132-3p to be a target for APTR, and its expression was demonstrated to be inhibited by APTR. In functional terms, knockdown of APTR and overexpression of miR-132-3p both, remarkably repressed human OS cell proliferation, invasion and migration, and induced apoptosis. Also, Yes-associated protein 1 (YAP1) was determined as an inhibitory target of miR-132-3p. Moreover, our findings demonstrated that the repression of YAP1 protein expression and the suppression of Ki-67, MMP9, and Bcl2 expression induced by APTR knockdown required increased miR-132-3p. Thus, APTR contributed to OS progression through repression of miR-132-3p and upregulation of YAP1 expression. Therefore, we have uncovered a novel regulatory mechanism by which the APTR/miR-132-3p/YAP1 axis can regulate OS progression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Ósseas/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Apoptose , Sítios de Ligação , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
5.
J Cell Biochem ; 120(4): 5495-5504, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30302813

RESUMO

MicroRNA-17-5p (miR-17-5p) and epithelial-mesenchymal transition (EMT) have been reported to participate in the development and progression of multiple cancers. However, the relationship between the miR-17-5p and EMT in osteosarcoma (OS) is still poorly understood. This study was to investigate the effects of the miR-17-5p and its potential mechanism in regulating proliferation, apoptosis, and EMT of human OS. Quantitative real-time PCR was used to detect the miR-17-5p and SRC kinase signaling inhibitor 1 (SRCIN1) messenger RNA expression in OS specimens and cell lines. After transfection with miR-17-5p inhibitors, proliferation, apoptosis, migration, and invasion of OS cells were assessed by using the Cell Counting Kit-8, the annexin V-FITC apoptosis, wound-healing, and transwell assays. The SRCIN1 was validated as a target of the miR-17-5p through bioinformatics algorithms and luciferase reporter assay. Moreover, the expression of EMT markers, E-cadherin, N-cadherin, and Snail was identified by the Western blot analysis. MiR-17-5p was significantly upregulated in OS tumor samples and cell lines. It inhibited proliferation and EMT, and promoted apoptosis in OS. The SRCIN1 was identified as a direct target of the miR-17-5p. Silenced miR-17-5p could change the expression of EMT markers, such as upregulating the expression of E-cadherin, and downregulating the expression of N-cadherin and Snail through targeting the antioncogenic SRCIN1. These findings suggest that the miR-17-5p promotes cell proliferation, and EMT in human OS by directly targeting the SRCIN1, and reveal a branch of the miR-17-5p/SRCIN1/EMT signaling pathway involved in the progression of OS.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/biossíntese , Neoplasias Ósseas/metabolismo , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Osteossarcoma/metabolismo , RNA Neoplásico/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Feminino , Humanos , Masculino , MicroRNAs/genética , Proteínas de Neoplasias/genética , Osteossarcoma/genética , Osteossarcoma/patologia , RNA Neoplásico/genética
6.
J Cell Physiol ; 233(8): 6041-6051, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29319166

RESUMO

A growing number of long non-coding RNAs (lncRNAs) have been found to be involved in diverse biological processes such as cell cycle regulation, embryonic development, and cell differentiation. However, limited knowledge is available concerning the underlying mechanisms of lncRNA functions. In this study, we found down-regulation of TCONS_00041960 during adipogenic and osteogenic differentiation of glucocorticoid-treated bone marrow mesenchymal stem cells (BMSCs). Furthermore, up-regulation of TCONS_00041960 promoted expression of osteogenic genes Runx2, osterix, and osteocalcin, and anti-adipogenic gene glucocorticoid-induced leucine zipper (GILZ). Conversely, expression of adipocyte-specific markers was decreased in the presence of over-expressed TCONS_00041960. Mechanistically, we determined that TCONS_00041960 as a competing endogenous RNA interacted with miR-204-5p and miR-125a-3p to regulate Runx2 and GILZ, respectively. Overall, we identified a new TCONS_00041960-miR-204-5p/miR-125a-3p-Runx2/GILZ axis involved in regulation of adipogenic and osteogenic differentiation of glucocorticoid-treated BMSCs.


Assuntos
Adipogenia/genética , Células da Medula Óssea/fisiologia , Células-Tronco Mesenquimais/fisiologia , MicroRNAs/genética , Osteogênese/genética , RNA Longo não Codificante/genética , Adipócitos/fisiologia , Animais , Diferenciação Celular/genética , Regulação para Baixo/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/genética
7.
Future Oncol ; 14(29): 3015-3022, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29987950

RESUMO

AIM: To investigate the expression level of lncRNA MALAT1 in papillary thyroid cancer (PTC) and evaluate its clinical diagnostic value as a biomarker in PTC. METHODS: MALAT1 lncRNA expression in tissues was detected by qRT-PCR. The diagnostic value of MALAT1 as a biomarker in PTC was evaluated with receiver operating characteristics. RESULTS: MALAT1 expression was upregulated in PTC tissues compared with paired corresponding noncancerous tissues. We also found that upregulated MALAT1 expression was correlated with tumor size, lymph node metastases (p = 0.011) and WHO disease stage. The area under the curve was 0.6320, 0.7192, 0.7089 and 0.7000 for PTC, lymph node metastasis, extrathyroidal extension and WHO disease stage prediction, respectively. CONCLUSION: Our finding suggests that MALAT1 may exert oncogenic function in PTC and may be a potential diagnostic marker for this cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/metabolismo , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Análise Serial de Tecidos , Regulação para Cima
8.
Tumour Biol ; 37(11): 15211-15220, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27683056

RESUMO

MicroRNAs (miRNAs) can function as oncogenes or tumor suppressor genes and are involved in multiple processes in cancer development and progression. For example, miR-192 is dysregulated in multiple human cancers, including osteosarcoma (OS). However, the pathophysiological role of miR-192 and its relevance to OS cell growth and invasion has not yet been clarified. This study aimed to investigate the expression of miR-192 in OS and elucidate the molecular mechanisms by which miR-192 acts as a tumor suppressor in this disease. The qRT-PCR data identified significant down-regulation of miR-192 in 20 OS tissue samples and two OS cell lines when compared with adjacent normal tissues and a human osteoblast cell line, respectively. Furthermore, Western blot analysis revealed overexpression of T cell-specific transcription factor (TCF) 7 protein in tumor tissues compared with matched adjacent normal tissues. Further in vitro studies demonstrated that enforced expression of miR-192 inhibited U2OS and MG63 cell proliferation, invasion, and migration and induced apoptosis. Finally, Western blot and Luciferase assays identified TCF7 as a target of miR-192. Collectively, these findings suggest an important role for miR-192 in regulating the proliferation, migration, invasion, and apoptosis of OS cells through the regulation of TCF7.


Assuntos
Neoplasias Ósseas/patologia , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/patologia , Fator 1 de Transcrição de Linfócitos T/metabolismo , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Estudos de Casos e Controles , Humanos , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator 1 de Transcrição de Linfócitos T/genética , Células Tumorais Cultivadas
9.
Sci Rep ; 13(1): 10230, 2023 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353555

RESUMO

The present work aimed to establish a new model to accurately estimate overall survival (OS) as well as cancer-specific survival (CSS) of osteosarcoma. Osteosarcoma cases were collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2017 and randomized as training or validation sets. Then, the OS- and CSS-related variables were discovered through multivariate Cox regression analysis to develop new nomograms to predict the 1-, 3- and 5-year OS and CSS. Besides, consistency index (C-index), decision curve analysis (DCA), along with calibration curve were adopted for assessing the predicting ability of our constructed nomograms after calibrating for 1-, 3- and 5-year OS and CSS. Altogether, 1727 osteosarcoma cases were enrolled in the present study and randomly divided as training (n = 1149, 70%) or validation (n = 576, 30%) set. As shown by univariate as well as multivariate Cox regression analyses, age, grade, T stage, M stage, surgery, chemotherapy, and histological type were identified to be the adverse factors to independently predict OS and CSS among the osteosarcoma cases. Besides, based on results of multivariate Cox regression analysis, we constructed the OS and CSS prediction nomograms. The C-index in training set was 0.806 (95% CI 0.769-0.836) for OS nomogram and 0.807 (95% CI 0.769-0.836) for CSS nomogram. In the meantime, C-index value in validation set was 0.818 (95% CI 0.789-0.847) for OS nomogram, while 0.804 (95% CI 0.773-0.835) for CSS nomogram. Besides, those calibration curves regarding the 3- and 5-year CSS of our constructed nomogram were highly consistent between the predicted values and the measurements in the training set as well as the external validation set. Our constructed nomogram outperformed the TNM stage in prediction. Our constructed nomogram is facile, creditable, and feasible; it efficiently predicts OS and CSS for osteosarcoma cases and can assist clinicians in assessing the prognosis for individuals and making decisions.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Nomogramas , Osteossarcoma/terapia , Pacientes , Calibragem , Programa de SEER , Prognóstico , Estadiamento de Neoplasias
10.
Cancer Med ; 12(1): 445-458, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35655441

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) have critical functions within esophageal squamous cell carcinoma (ESCC). However, the function and mechanism underlying ESCC-associated lncRNA-1 (ESCCAL-1) in ESCC tumorigenesis have not been well clarified. METHODS: ESCCAL-1, miR-590 and LRP6 were quantified using qRT-PCR. Cell viability, migration and invasion abilities were measured using CCK-8 assay and transwell assays. The protein pression was determined with western blot assay. The xenograft model assays were used to examine the impact of ESCCAL-1 on tumorigenic effect in vivo. Direct relationships among ESCCAL-1, miR-590 and LRP6 were confirmed using dual-luciferase reporter assays. RESULTS: The present work discovered the ESCCAL-1 up-regulation within ESCC. Furthermore, ESCCAL-1 was found to interact with miR-590 and consequently restrict its expression. Functionally, knocking down ESCCAL-1 or over-expressing miR-590 hindered ESCC cell growth, invasion, and migration in vitro. Moreover, inhibition of miR-590 could reverse the effect of knockdown of ESCCAL-1 on cells. Importantly, it was confirmed that LRP6 was miR-590's downstream target and LRP6 over-expression also partly abolished the role of miR-590 overexpression in ESCC cells. CONCLUSION: We have uncovered a novel regulatory network comprising aberrant interaction of ESCCAL-1/miR-590/LRP6 participated in ESCC progression.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Esofágicas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo
11.
Oncol Rep ; 44(4): 1385-1392, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945478

RESUMO

MicroRNA­590 (miR­590) has been revealed as a tumor suppressor, while low­density lipoprotein receptor­related protein 6 (LRP6) is considered to act as a tumor promoter. However, their roles and underlying molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC) have yet to be fully elucidated. Therefore, the present study aimed to investigate these mechanisms. The expression levels of miR­590 and LRP6 in human ESCC samples and cell lines were determined using reverse transcription­quantitative PCR. Bioinformatics analysis was used to predict the relationship between miR­590 and LRP6, and luciferase assay was performed to validate the relationship between these factors. Transwell assays were used to determine cell migration and invasion, while western blotting assays were used to detect the protein expression levels of LRP6, E­cadherin, N­cadherin and Vimentin. The present study demonstrated that miR­590 was downregulated and LRP6 was upregulated in ESCC tissues and cell lines. Furthermore, it was found that miR­590 overexpression and LRP6 knockdown inhibited cell migration, invasion and epithelial­to­mesenchymal transition (EMT) in ESCC cell lines. Additional mechanistic studies identified that LRP6 was a target of, and was inhibited by, miR­590. Collectively, the present findings suggested that miR­590 inhibited the invasion, migration and EMT of ESCC cells by mediating LRP6.


Assuntos
Movimento Celular/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , MicroRNAs/genética , Adulto , Idoso , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Vimentina/genética
12.
Cancer Lett ; 493: 217-227, 2020 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-32905814

RESUMO

The expression of lncRNA ESCCAL-1 is upregulated in esophageal squamous cell carcinoma (ESCC). However, the molecular pathways regulated by ESCCAL-1 in esophageal cancer remain obscure. We found that high expression of the lncRNA ESCCAL-1 in human ESCC tumors correlated with worse clinicopathologic features. Furthermore, depletion of ESCCAL-1 in ESCC models inhibited the cellular processes associated with malignancy, including proliferation, migration and invasion, resistance to apoptosis, and impaired tumor growth in mice. Using a combinatorial approach, we discovered that ESCCAL-1 regulates malignant phenotypes in ESCC by acting as a molecular sponge for miR-590-3p. This interaction prevents miR-590-3p from suppressing APOBEC3G expression. Increased APOBEC3G was also a biomarker of worse clinicopathologic features in human ESCC tumors. Depletion of ESSCAL-1 or APOBEC3G, or overexpression of miR-590-3p resulted in increased apoptosis due to downregulation of the PI3K/Akt signaling. This study demonstrates that the lncRNA ESCCAL-1 promotes malignant features of ESCC by relieving the inhibitory effect of miR-590-3p on APOBEC3G expression and identifies potential biomarkers or therapeutic targets to improve ESCC treatment outcomes.


Assuntos
Desaminase APOBEC-3G/genética , Regulação para Baixo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Desaminase APOBEC-3G/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico
13.
Am J Transl Res ; 11(4): 2507-2515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105858

RESUMO

AIM: To determine whether VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 genotypes contribute to warfarin therapy in patients during initiation and maintenance anticoagulation treatment after heart valve surgery. METHODS: 287 Chinese patients with warfarin treatment more than three month after heart valve replacement operations were enrolled. Blood was collected from each subject for DNA extraction and genotyping. Analyzing the relationship between genotypes and warfarin curative effect. RESULTS: Their mean age was 48.0 ± 10.5 years old. During the initiation phase, the growth rate of INR was partial correlated with VKORC1 rs9923231, CYP2C9 rs1057910 and ORM1 rs17650, respectively. Compared with AG or GG genotypes of VKORC1 c.-1639 carriers, patients with VKORC1 c.-1639AA reached target INR therapeutic range faster (P<0.001) and has a high risk of overanticoagulation (P<0.001). Carriers of at least one CYP2C9 *3 allele reached the target INR therapeutic range and supra-therapeutic INR were faster than CYP2C9 wild-type carriers (P=0.032, P=0.032, respectively). CYP4F2 rs2108622 could significantly influence on time to the target INR therapeutic range and time to INR above 3.0 after hierarchical analysis with VKORC1, CYP2C9 and ORM1 (P=0.011, P=0.044, respectively). VKORC1 rs9923231, CYP2C9 rs1057910 and ORM1 rs17650 were significantly influence the %TTR in three months (P=0.031, P=0.008, P=0.001, respectively). During the maintenance phase, VKORC1 c.-1639AA carriers spent more time at supra-therapeutic INRs (P<0.001). CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 gene variants did not affect outcome parameters in maintenance phase. CONCLUSIONS: This study found that genetic factors could significantly affected on warfarin therapy in Chinese. Meanwhile, genetic variations play a more important role in the initial phase than did in maintenance phase of warfarin therapy.

14.
Infect Drug Resist ; 11: 29-36, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29379306

RESUMO

OBJECTIVES: Teicoplanin, an antibiotic, has poor clinical efficacy when using the current drug label's recommended regimen, which is approved by the China Food and Drug Administration. This study explores the appropriate loading and maintenance doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough concentration (minimum concentration [Cmin]). SUBJECTS AND METHODS: All patients treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central Hospital were screened for enrollment. A total of 113 subjects were included and then divided into four groups: A (received three to six doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B (received three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D (received one to three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were detected with high-performance liquid chromatography on day 4, 30 minutes before maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were compared among the four groups. RESULTS: Mean Cmin differed significantly among the four groups (A, 18.11±6.37 mg/L; B, 15.91±4.94 mg/L; C, 17.06±5.66 mg/L; D, 11.97±3.76 mg/L) (P<0.001), with creatinine clearance of 89.62 (53.72-162.48), 49.66 (40.69-59.64), 27.17 (9.7-39.45), and 96.6 (17.63-394.73) mL/min, respectively. The ratio of loading dose for 3 days to creatinine clearance and serum Cmin were significantly correlated (R=0.59, P<0.001). The correlation between the estimated probability of success and teicoplanin Cmin was assessed using binary logistic regression (OR 2.049, P<0.001). Hepatotoxicity- and nephrotoxicity-incidence rates did not significantly differ among the four groups (P=0.859 and P=0.949, respectively). CONCLUSION: A loading dose of 400 mg at 12-hour intervals three to six times is needed to achieve the early target range (15-20 mg/L) and improve the clinical efficacy rate for normal-renal-function patients. It is urgently necessary to amend the drug label for the recommended regimen.

15.
Onco Targets Ther ; 11: 4893-4899, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147340

RESUMO

BACKGROUND: This study was designed to research the potential function of lncRNA ANRIL in osteosarcoma (OS). MATERIALS AND METHODS: Quantitative real-time PCR, cell counting kit-8, wound healing assay, Transwell assay, flow cytometric analysis, caspase activity analysis, and Western blot were carried out. RESULTS: ANRIL was remarkably upregulated in human OS tissues and cells, and knockdown of ANRIL significantly suppressed MG63 cell proliferation, migration, and invasion and promoted apoptosis. Moreover, our mechanistic research findings verified that ANRIL-influenced growth and apoptosis may be partly through regulation of caspase-3 and Bcl-2. Migration and invasion were influenced via ANRIL-mediated regulation of MTA1, TIMP-2, and E-cadherin. CONCLUSION: Our finding demonstrates that ANRIL plays vital roles in OS growth and metastasis.

16.
Eur J Pharmacol ; 783: 33-46, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27108788

RESUMO

Velvet antlers (VAs) are commonly used in traditional Chinese medicine and invigorant and contain many functional components for health promotion. The velvet antler peptide sVAP32 is one of active components in VAs; based on structural study, the sVAP32 interacts with TGF-ß1 receptors and disrupts the TGF-ß1 pathway. We hypothesized that sVAP32 prevents cardiac fibrosis from pressure overload by blocking TGF-ß1 signaling. Sprague-Dawley rats underwent transverse aortic constriction (TAC) or a sham operation. After one month, rats received either sVAP32 (15mg/kg/day) or vehicle for an additional one month. TAC surgery induced significant cardiac dysfunction, fibroblast activation and fibrosis; these effects were improved by treatment with sVAP32. In the heart tissue, TAC remarkably increased the expression of TGF-ß1 and connective tissue growth factor (CTGF), reactive oxygen species levels, and the phosphorylation levels of Smad2/3 and extracellular signal-regulated kinases 1/2 (ERK1/2). SVAP32 inhibited the increases in reactive oxygen species levels, CTGF expression and the phosphorylation of Smad2/3 and ERK1/2, but not TGF-ß1 expression. In cultured cardiac fibroblasts, angiotensin II (Ang II) had similar effects compared to TAC surgery, such as increases in α-SMA-positive cardiac fibroblasts and collagen synthesis. SVAP32 eliminated these effects by disrupting TGF-ß1 binding to its receptors and blocking Ang II/TGF-ß1 downstream signaling. These results demonstrated that sVAP32 has anti-fibrotic effects by blocking the TGF-ß1 pathway in cardiac fibroblasts.


Assuntos
Chifres de Veado/química , Pressão Sanguínea/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Peptídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Sequência de Aminoácidos , Angiotensina II/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertrofia/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Vasoconstrição/efeitos dos fármacos
17.
Sci Rep ; 6: 38491, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27910957

RESUMO

The imbalance between adipogenic and osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) plays a significant role in the pathogenesis of steroid-induced osteonecrosis of the femoral head (ONFH). Several microRNAs (miRNAs) are involved in regulating adipogenesis and osteogenesis. In this study, we established a steroid-induced ONFH rat model to identify the potential relevant miRNAs. We identified 9 up-regulated and 28 down-regulated miRNAs in the ONFH rat model. Of these, miR-27a was down-regulated and negatively correlated with peroxisome proliferator-activated receptor gamma (PPARγ) and gremlin 1 (GREM1) expression. Further studies confirmed that PPARγ and GREM1 were direct targets of miRNA-27a. Additionally, adipogenic differentiation was enhanced by miR-27a down-regulation, whereas miRNA-27a up-regulation attenuated adipogenesis and promoted osteogenesis in steroid-induced rat BMSCs. Moreover, miRNA-27a up-regulation had a stronger effect on adipogenic and osteogenic differentiation in steroid-induced rat BMSCs than si-PPARγ and si-GREM1. In conclusion, we identified 37 differentially expressed miRNAs in the steroid-induced ONFH model, of which miR-27a was down-regulated. Our results showed that miR-27a up-regulation could inhibit adipogenesis and promote osteogenesis by directly targeting PPARγ and GREM1. Thus, miR-27a is likely a key regulator of adipogenesis in steroid-induced BMSCs and a potential therapeutic target for ONFH treatment.


Assuntos
Adipogenia/genética , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Osteogênese/genética , PPAR gama/metabolismo , Proteínas/metabolismo , Esteroides/farmacologia , Regiões 3' não Traduzidas/genética , Adipogenia/efeitos dos fármacos , Animais , Sequência de Bases , Citocinas , Modelos Animais de Doenças , Regulação para Baixo/genética , Feminino , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Perfilação da Expressão Gênica , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Esteroides/efeitos adversos , Regulação para Cima/genética
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