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1.
J Environ Pathol Toxicol Oncol ; 38(3): 195-203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679307

RESUMO

UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/ß-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-ß/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/ß-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/ß-catenin signal pathway and migration by TGF-ß/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/farmacologia , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Organismos Livres de Patógenos Específicos
2.
Medicine (Baltimore) ; 98(43): e17432, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651846

RESUMO

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.


Assuntos
Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/sangue , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
3.
Medicine (Baltimore) ; 98(42): e17412, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626095

RESUMO

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated. METHODS: The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model. RESULTS: CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan-Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273-8.775, P = .021). CONCLUSIONS: Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.


Assuntos
Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética
4.
Cytogenet Genome Res ; 158(4): 205-212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31434093

RESUMO

EHMT2 (euchromatic histone lysine methyltransferase 2), a histone methyltransferase, has been shown to be involved in multiple human cancers. In this study, we determined mRNA and protein expression of EHMT2 in cervical cancer cells and normal cervical epithelial cells. EHMT2 was inhibited with short hairpin RNA (shEHMT2) in cervical cancer cells. Cell viability, colony proliferation, apoptosis, adhesion, and invasion assays and Western blot were performed to assess the function of EHMT2. As a result, EHMT2 was upregulated in human cervical cancer cells compared to normal cervical epithelial cells. Suppression of EHMT2 expression impairs cell proliferation and induces apoptosis. Furthermore, EHMT2 silencing inhibited cell adhesion and invasion. Finally, knockdown of EHMT2 resulted in a reduction of the expression of the tumorigenic proteins Bcl-2, Mcl-1, and Survivin and in an increase in the expression of the anti-malignant protein E-cadherin. In conclusion, our data suggest that EHMT2 plays a key role in cell proliferation and metastatic capacity in cervical cancer cells and could serve as a potential therapeutic target.


Assuntos
Inativação Gênica , Antígenos de Histocompatibilidade/genética , Histona-Lisina N-Metiltransferase/deficiência , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologia , Apoptose/genética , Caderinas/biossíntese , Adesão Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Antígenos de Histocompatibilidade/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Invasividade Neoplásica/patologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/prevenção & controle , Neoplasias do Colo do Útero/genética
5.
Life Sci ; 234: 116771, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421084

RESUMO

AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/genética , Neoplasias Ósseas/patologia , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/secundário , Osteossarcoma/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Animais , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/genética , Regulação para Cima , Adulto Jovem
6.
Anticancer Res ; 39(8): 4561-4568, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366560

RESUMO

BACKGROUND/AIM: Neoplastic spindle cells (NSCs) are believed to play a role in cancer invasion and metastasis, as well as in poor prognosis. The clinicopathological characteristics and prognostic relevance of NSCs was investigated in gallbladder cancer. MATERIALS AND METHODS: Specimens were obtained from 62 patients with gallbladder cancer who underwent surgery. The emergence of NSCs and their correlation with clinicopathological factors, prognosis, and EMT markers was evaluated. RESULTS: The NSC grade correlated with tumor size, preoperative CA19-9, surgical margin, the degree of differentiation, the depth of invasion, lymph node metastasis, lymphatic invasion, vascular invasion, and perineural invasion. Multivariate analysis of overall survival showed that NSCs were an independent prognostic factor. A correlation between NSCs and EMT was also suggested. CONCLUSION: NSCs are an independent prognostic factor for patients with postoperative gallbladder cancer, which also suggests a correlation between NSCs and EMT.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Vesícula Biliar/patologia , Invasividade Neoplásica/patologia , Prognóstico , Adulto , Idoso , Antígeno CA-19-9/sangue , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
7.
Anticancer Res ; 39(8): 4149-4164, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366500

RESUMO

BACKGROUND/AIM: Signaling regulation of myeloid zinc finger 1 (MZF1) has been implicated in the progression of many human malignancies; however, the mechanistic action of MZF1 in triple-negative breast cancer (TNBC) progression remains elusive. In this study, the aim was to investigate the molecular mechanisms of MZF1 and its functional role in TNBC cellular migration and invasion. MATERIALS AND METHODS: Hs578T and MDA-MB-231 cells were transfected to stably express the acidic domain of MZF1 (MZF160-72), or were transfected with MZF1-specific or ELK1-specific short hairpin RNA (shRNA). Changes in cell morphology and distributions of cellular proteins were observed and subsequently migration and invasion were measured by wound healing and transwell assays. Expression levels of epithelial-mesenchymal transition (EMT)-related genes were carried out using immunoblotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. Data of transcriptional regulation were obtained from promoter-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. RESULTS: Herein, we found that MZF1 in high-level MZF1-expressing TNBC cells is associated with cell migration, invasion, and mesenchymal phenotype. MZF1 interacted with the promoter region of insulin-like growth factor 1 receptor (IGF1R) to drive invasion and metastasis of high-level MZF1-expressing TNBC cells. Exogenous expression of the acidic domain of MZF1 repressed the binding of endogenous MZF1 to IGF1R promoter via blocking the interaction with ETS-like gene 1 (ELK1). This blockage not only caused MZF1 protein degradation, but also restrained ELK1 nuclear localization in high-level MZF1-expressing TNBC cells. MZF1, but not ELK1, was necessary for the retention of mesenchymal phenotype by repressing IGF1R promoter activity in TNBC cells expressing high levels of MZF1. Activation of the IGF1R-driven p38MAPK-ERα-slug-E-cadherin signaling axis mediated the conversion of mesenchymal cell to epithelial phenotype, caused by MZF1 destabilization. These results suggest that MZF1 is an oncogenic inducer. CONCLUSION: Blocking of the MZF1/ELK1 interaction to reduce MZF1 protein stability by saturating the endogenous MZF1/ELK1 binding domains might be a promising therapeutic strategy for the treatment of high-level MZF1-expressing TNBC.


Assuntos
Fatores de Transcrição Kruppel-Like/genética , Receptores de Somatomedina/genética , Neoplasias de Mama Triplo Negativas/genética , Proteínas Elk-1 do Domínio ets/genética , Caderinas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , Receptor alfa de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Regiões Promotoras Genéticas/genética , Domínios Proteicos/genética , Transdução de Sinais/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
8.
Anticancer Res ; 39(8): 4325-4328, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366524

RESUMO

BACKGROUND/AIM: The significance of second transurethral resection (TUR), and identification of predictive factors for residual cancer remain unrevealed. This study aimed to find residual cancer and up-staging rates, as well as predictive factors for residual cancer, in patients who undergo second TUR for non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent second TURs for NMIBC between 2015 and 2017, were included in the study and their clinicopathological characteristics were analyzed for predictors of residual cancer. RESULTS: Among 143 Japanese patients whose tumors were initially diagnosed as high-risk NMIBC, residual cancers detected at second TURs were, Tis: n=22 (15.4%), Ta: n=15 (10.5%) and T1: n=29 (20.3%). No patients showed up-staging from NMIBC to MIBC. The presence of carcinoma-in situ at initial TUR was an independent risk factor for any residual cancer (Tis, Ta and T1), non-flat residual cancer (Ta and T1), and flat residual cancer (Tis). CONCLUSION: The presence of carcinoma-in situ is suggested to be an independent predictor of residual cancer. This may help guide decisions to perform second TUR.


Assuntos
Carcinoma in Situ/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Cistectomia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasia Residual/diagnóstico , Neoplasia Residual/patologia , Fatores de Risco , Resultado do Tratamento , Uretra/patologia , Uretra/cirurgia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Procedimentos Cirúrgicos Urológicos
9.
Cancer Sci ; 110(9): 2960-2972, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301086

RESUMO

In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin-coupled microRNA capture were carried out to investigate the Ago2-dependent interaction of circCRIM1 and microRNA (miR)-93/miR-182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well-known tumor suppressor, by sponging miR-93 and miR-182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , RNA/genética , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Sci ; 110(9): 2760-2772, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325400

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. TP53TG1 is a recently identified lncRNA and several studies have shown that TP53TG1 may play the role of tumor suppressor gene or oncogene in different tumors. Nevertheless, the involvement of TP53TG1 in carcinogenesis of pancreatic ductal adenocarcinoma (PDAC) has not been characterized. In our studies, we identified that TP53TG1 was highly expressed in PDAC and was a novel regulator of PDAC development. Knockdown of TP53TG1 inhibited proliferation, induced apoptosis, and decreased migration and invasion in PDAC cells, whereas enhanced expression of TP53TG1 had the opposite effects. Mechanistically, TP53TG1 could directly bind to microRNA (miR)-96 and effectively function as a sponge for miR-96, thus antagonizing the functions of miR-96 and leading to derepression of its endogenous target KRAS, which is a core oncogene in the initiation and maintenance of PDAC. Taken together, these observations imply that TP53TG1 contributes to the growth and progression of PDAC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-96 and regulate KRAS expression, which highlights the importance of the complicated miRNA-lncRNA network in modulating the progression of PDAC.


Assuntos
Carcinoma Ductal Pancreático/genética , Proteínas de Ligação a DNA/metabolismo , MicroRNAs/antagonistas & inibidores , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Longo não Codificante/metabolismo , Carcinogênese/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA Longo não Codificante/genética
11.
Medicine (Baltimore) ; 98(27): e16009, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277094

RESUMO

Bladder cancer is one of the most common malignancies of urinary tract. The current study aimed to investigate the role of insulin-like growth factor II messenger RNA binding protein 3 (IMP3) expression in the prognostic evaluation of non-muscle- invasive urothelial carcinoma of the bladder.Immunohistochemistry (IHC) was carried out to examine IMP3 protein expression in specimens from 183 cases of non-muscle-invasive urothelial carcinoma, 20 cases of muscle-invasive urothelial carcinoma and 20 benign tissues adjacent to cancer tissue.The expression of IMP3 was not detected in the adjacent benign tissues. The expression intensity of IMP3 in muscle-invasive samples was significantly higher than that in non-muscle-invasive urothelial carcinoma specimens (P = .008). IMP3 expression was significantly related with advanced tumor stage (P < .001), advanced tumor grade (P = .004), and tumor recurrence (P < .001) in non-muscle-invasive urothelial carcinomas. Kaplan-Meier analysis showed that IMP3-positive patients had much lower disease-free (P < .001), progression-free (P = .002) and metastasis-free (P = .019) survival rates compared with those with IMP3-negative tumors. By multivariable Cox analysis, we also found that IMP3 expression in non-muscle- invasive urothelial carcinomas proved to be an independent unfavorable prognostic factor of disease-free survival (HR: 2.52; 95% CI, 1.39-4.56; P = .002), progression- free survival (HR: 5.19; 95% CI, 1.54-17.46; P = .008) and metastasis-free survival (HR: 4.87; 95% CI, 1.08-22.02; P = .040).Our results demonstrate that the expression of IMP3 in non-muscle- invasive bladder cancer can serve as an independent predictor that will help recognize the subgroup of patients with a high ability to relapse, progress, and metastasize and who might get the maximum benefit from an early and more aggressive treatment strategy.


Assuntos
Carcinoma de Células de Transição/genética , Proteínas de Ligação a RNA/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Modelos de Riscos Proporcionais , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
12.
Gen Physiol Biophys ; 38(4): 295-304, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31241046

RESUMO

Glioma is a serious malignant tumor without effective therapies till now. lncRNA PEG10 was reported to have some biological activities in cancers. Hence, we explored the effects of PEG10 on the human glioma cell line U251 cells. U251 cells were transfected with sh-PEG10 and/or miR-506 inhibitor. The expression of PEG10 and miR-506 was measured by qRT-PCR. Cell viability, cell apoptosis, cell migration and invasion were detected by CCK-8 assay, flow cytometry and Transwell chamber assay, respectively. The cell proliferation and apoptosis related p16, p53, Bcl-2, Bax, and pro-/Cleaved-Caspase-3/9, migration and invasion related-protein: matrix metalloproteinases MMP-2, MMP-9 and vimentin, and Raf/MEK/ERK and JAK1/STAT3 pathways-related proteins were accessed by Western blot. Transfection with sh-PEG10 inhibited cell viability, migration and invasion, and increased cell apoptosis. Meanwhile, PEG10 silence upregulated the expression of p16 and p53, Bax, cleaved-Caspase-3/9 expression, and downregulated Bcl-2 expression. PEG10 silence upregulated miR-506 expression. Co-transfection with sh-PEG10 and miR-506 inhibitor impaired the tumor suppressive effects. PEG10 knockdown decreased the phosphorylation of Raf/MEK/ERK and JAK1/STAT3-related proteins Raf, MEK, ERK, JAK1 and STAT3. PEG10 knockdown inhibited cell viability, migration and invasion, induced cell apoptosis through miR-506 upregulation, as well as inactivation of Raf/MEK/ERK and JAK1/STAT3 signal pathways.


Assuntos
Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/patologia , MicroRNAs/genética , Invasividade Neoplásica/genética , Proteínas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioma/genética , Humanos , MicroRNAs/biossíntese
13.
Cancer Immunol Immunother ; 68(7): 1157-1169, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31197461

RESUMO

Chordoma is difficult to eradicate due to high local recurrence rates. The immune microenvironment is closely associated with tumor prognosis; however, its role in skull base chordoma is unknown. The expression of Galectin-9 (Gal9) and tumor-infiltrating lymphocyte (TIL) markers was assessed by immunohistochemistry. Kaplan-Meier and multivariate Cox analyses were used to assessing local recurrence-free survival (LRFS) and overall survival (OS) of patients. MiR-455-5p was identified as a regulator of Gal9 expression. Immunopositivity for Gal9 was associated with tumor invasion (p = 0.019), Karnofsky performance status (KPS) score (p = 0.017), and total TIL count (p < 0.001); downregulation of miR-455-5p was correlated with tumor invasion (p = 0.017) and poor prognosis; and the T-cell immunoglobulin and mucin-domain 3 (TIM3)+ TIL count was associated with chordoma invasion (p = 0.010) and KPS score (p = 0.037). Furthermore, multivariate analysis indicated that only TIM3+ TIL density was an independent prognostic factor for LRFS (p = 0.010) and OS (p = 0.016). These results can be used to predict clinical outcome and provide a basis for immune therapy in skull base chordoma patients.


Assuntos
Cordoma/patologia , Galectinas/genética , Linfócitos do Interstício Tumoral/imunologia , MicroRNAs/metabolismo , Neoplasias da Base do Crânio/patologia , Adolescente , Adulto , Idoso , Criança , Cordoma/genética , Cordoma/imunologia , Cordoma/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Galectinas/imunologia , Galectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/imunologia , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/imunologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Base do Crânio/imunologia , Neoplasias da Base do Crânio/mortalidade , Análise de Sobrevida , Adulto Jovem
14.
Genet Test Mol Biomarkers ; 23(6): 409-417, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31161818

RESUMO

Aim: Cervical cancer is the most common gynecological cancer. Recent studies have revealed that the F-box and WD repeat domain containing 7 (FBXW7) gene, which encodes a subunit of Skp1-Cul1-F-box protein (SCF) ubiquitin ligase, is frequently mutated in cervical squamous cell carcinomas. In this study, we investigated whether Chinese cervical cancer cells also harbor these mutations. Methods: Using PCR and sequencing assays, a total of 190 specimens from Han Chinese patients with cervical cancer were analyzed for FBXW7 mutations. Results: Two FBXW7 mutations (p.R479P and p.L443H), were identified from a study of 145 (1.4%) cervical squamous cell carcinomas. The p.L443H somatic mutation has not been previously reported. Functional assays showed that both of these FBXW7 mutations could promote cell proliferation, migration, and invasion. Conclusion: A low frequency (1.4%) of cervical squamous cell carcinomas were identified with FBXW7 mutations. We did, however, identify a novel FBXW7 mutation. Our results also demonstrated that the identified FBXW7 mutations could promote cell proliferation, migration, and invasion in cervical cancer cells.


Assuntos
Proteína 7 com Repetições F-Box-WD/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular , Movimento Celular/genética , Proliferação de Células/genética , China , Proteínas F-Box , Proteína 7 com Repetições F-Box-WD/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Mutação/genética , Invasividade Neoplásica/genética
15.
Cancer Biother Radiopharm ; 34(4): 258-263, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31070482

RESUMO

Background: Downregulation of LncRNA LINC-PINT has been observed in different types of cancer cells, indicating its role as a tumor suppressor. Materials and Methods: Expression of LINC-PINT and miRNA-21 in tumor tissues and adjacent healthy tissues of 56 patients with osteosarcoma was detected by real-time quantitative PCR. Correlations between expression levels of LncRNA LINC-PINT and miRNA-21 were analyzed by Pearson's correlation coefficient. Results: In this study, we found that LncRNA LINC-PINT was inhibited, whereas miRNA-21 was promoted in tumor tissues than in adjacent healthy tissues of patients with osteosarcoma. Expression levels of LncRNA LINC-PINT were affected by both tumor size and tumor metastasis. LncRNA LINC-PINT and miRNA-21 were significantly and reversely correlated in both tumor cells and adjacent healthy tissues. LncRNA LINC-PINT overexpression led to downregulated miRNA-21 expression in cancer cells, whereas miRNA-21 overexpression did not significantly affect LINC-PINT expression. Overexpression of LncRNA LINC-PINT inhibited whereas miRNA-21 overexpression promoted cancer cell proliferation, migration, and invasion. In addition, miRNA-21 overexpression partially rescued the inhibited cell proliferation, migration, and invasion mediated by LncRNA LINC-PINT overexpression. Conclusion: Therefore, LncRNA LINC-PINT may inhibit cancer cell proliferation, invasion, and migration in osteosarcoma by downregulating miRNA-21.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , RNA Longo não Codificante/metabolismo , Adolescente , Adulto , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Carga Tumoral/genética , Regulação para Cima , Adulto Jovem
16.
Cancer Biother Radiopharm ; 34(4): 264-270, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31070483

RESUMO

Purpose: Many studies have revealed that microRNAs (miRNAs) play crucial roles in cancer development and progression. miRNA-217 (miR-217) has been implicated in various cancers. However, the role of miR-217 in osteosarcoma (OS) remains unclear. In this study, the authors examined the role of miR-217 in development of OS. Materials and Methods: Using quantitative real-time PCR, they assessed expression levels of miR-217 in cultured cells and patient samples and examined the proliferation, migration, and invasion of cultured cells by MTT cell proliferation assays, cell scratch test, and cell transwell test. The proliferation, migration, and invasion were examined for MG63 and U2OS transfected by miR-217. Silent information regulator 2 homolog 1 (SIRT1) overexpression plasmid was designed. Results: Expression of miR-217 was downregulated in samples of OS tissue and cultured cells. Proliferation, migration, and invasion were inhibited by ectopic overexpression of miR-217. SIRT1 was identified as targets of miR-217. Expression levels of SIRT1 were inhibited by miR-217 expression in cultured cells, and the expression levels of miR-217 and SIRT1 were inversely correlated in patients with OS. Conclusion: MiR-217 acts as a tumor suppressor in the development of OS. The tumor-suppressive function of miR-217 in OS suggests inhibition of SIRT1.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Osteossarcoma/genética , Sirtuína 1/genética , Osso e Ossos/patologia , Osso e Ossos/cirurgia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Regulação para Cima
17.
Biomed Res Int ; 2019: 2304128, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058185

RESUMO

Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio [HR] 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.


Assuntos
Neoplasias da Mama/epidemiologia , Gerenciamento Clínico , Filogeografia/métodos , Prognóstico , Algoritmos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Receptor alfa de Estrogênio/genética , Feminino , Terapia de Reposição Hormonal , Humanos , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Receptor ErbB-2/genética , Receptores de Progesterona/genética
18.
Biomed Res Int ; 2019: 8650846, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31058194

RESUMO

Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient's quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF-κB signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF-κB signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer.


Assuntos
Neoplasias Ósseas/genética , MicroRNAs/genética , Osteogênese/genética , Neoplasias da Próstata/genética , Animais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Catepsina K/genética , Diferenciação Celular/genética , Exossomos/metabolismo , Exossomos/patologia , Regulação Neoplásica da Expressão Gênica/genética , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Fatores de Transcrição NFATC/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Osteoclastos/patologia , Células PC-3 , Neoplasias da Próstata/patologia , Transdução de Sinais/genética , Fosfatase Ácida Resistente a Tartarato/química , Fosfatase Ácida Resistente a Tartarato/genética
19.
Zhonghua Zhong Liu Za Zhi ; 41(5): 338-345, 2019 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-31137166

RESUMO

Objective: To detect the effect and regulatory mechanism of human ether à go-go related gene 1 (Herg 1) knockdown on the proliferation and invasion of osteosarcoma (OS). Methods: We constructed a recombinant adenovirus vector (Ad5-Herg1-shRNA) expressing short hair RNA (shRNA) against Herg1 and tested the knockdown efficiency. Then, the effects of Herg 1 knockdown on the proliferation, growth and invasion of osteosarcoma were measured by using cell counting kit-8 (CCK-8), wound healing assay, Transwell assay and xenograft model of nude mice, respectively. Tandem affinity purification, mass spectrometry and dual luciferase reporter assay were used to find out the molecules interacted with Herg1. Western blot was used to detect the expressions of large tumor suppressor gene (LATS1), p-LATS1, Yes-associated protein (YAP) and p-YAP in cells after infection of Ad5-Herg1-shRNA. Results: Compared to Ad5-control-shRNA, Ad5-Herg1-shRNA dramatically inhibited the expression of Herg1 in OS cells. The result of CCK8 array demonstrated that 143B cell vitalities of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (65.47±3.90)% and (79.90±1.52)%, significantly lower than (100.00±6.14)% of Ad5-control-shRNA group. Meanwhile, U2OS cell vitality of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (69.69±1.36)% and (76.72±2.75)%, significantly lower than (100.00±3.01)% of Ad5-control-shRNA group (all P<0.001). The results of wound healing array showed that 143B cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (33.03±2.88)% and (36.47±4.16)%, significantly lower than (97.78±2.28)% of Ad5-control-shRNA group. Meanwhile, U2OS cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were (68.07±0.90)% and (73.97±1.25)%, significantly lower than (96.50±1.12)% of Ad5-control-shRNA group (all P<0.001). The results of Transwell showed that 143B cell invasion numbers of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were 36.50±12.15 and 44.83±7.62, significantly lower than 195.33±19.68 of Ad5-control-shRNA group. Meanwhile, U2OS cell migration rates of Ad5-Herg1-shRNA1 and Ad5-Herg1-shRNA2 group were 21.83±7.99 and 22.85±7.08, significantly lower than 83.33±12.36 of Ad5-control-shRNA group (all P<0.001). The results of xenograft model of OS showed that the tumor volume and weight of Ad5-Herg1-shRNA group were significantly smaller than of Ad5-control-shRNA group after 14 days and 5 weeks of inoculation, respectively (P<0.001). Moreover, knockdown of Herg1 inhibited the metastasis of OS cells. In mechanism, Herg1 protein interacted with NF2 protein. Knockdown of Herg1 significantly suppressed the expression levels of LATS1 and YAP protein, and promoted the phosphorylation of LATS1 and YAP in OS cells (all P<0.001). Conclusion: Our findings suggest that Herg1 participates in the proliferation and motility of OS cells and may serve as a potential therapeutic target for osteosarcoma patients.


Assuntos
Neoplasias Ósseas/genética , Canal de Potássio ERG1/genética , Osteossarcoma/genética , Proteínas Serina-Treonina Quinases/metabolismo , Adenoviridae , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Regulação para Baixo , Vetores Genéticos , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Osteossarcoma/patologia , Transdução de Sinais , Transplante Heterólogo
20.
Nat Commun ; 10(1): 2115, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073170

RESUMO

Approximately 30% of ERα breast cancer patients relapse with metastatic disease following adjuvant endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain undergoes epigenetic reprogramming in aromatase inhibitors (AI)-resistant cells, leading to Keratin-80 (KRT80) upregulation. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion and cellular stiffening, collectively promoting cancer cell invasion. Shearwave elasticity imaging performed on prospectively recruited patients confirms KRT80 levels correlate with stiffer tumors. Immunohistochemistry showed increased KRT80-positive cells at relapse and, using several clinical endpoints, KRT80 expression associates with poor survival. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/patologia , Citoesqueleto/patologia , Queratinas Tipo II/genética , Recidiva Local de Neoplasia/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Citoesqueleto/genética , Resistencia a Medicamentos Antineoplásicos/genética , Elementos Facilitadores Genéticos/genética , Epigênese Genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Queratinas Tipo II/metabolismo , Células MCF-7 , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Domínios Proteicos/genética , Regulação para Cima
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