Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 39(11): 5963-5971, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704821

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate matrix metalloproteinase 11 (MMP11) as a promising biomarker in human pancreatic cancer. MATERIALS AND METHODS: A consecutive eliminating method was used to select biomarker candidates in pancreatic cancer. mRNA and protein expression levels of candidates were determined in tissues and whole blood samples of healthy donors and pancreatic cancer patients. The prognostic value of MMP11 was determined using various data-sets and Liptak's Z analysis. RESULTS: Analysis using Gene Expression Omnibus (GEO) database showed significantly higher MMP11 mRNA expression in pancreatic cancer tissues compared to that in various normal tissues. MMP11 protein was specifically expressed in pancreatic cancer tissues, but not in various normal or other cancer tissues. Secreted MMP11 levels could be measured using easily accessible techniques and whole blood samples of pancreatic cancer. In addition, high levels of MMP11 were associated with poor prognosis of pancreatic cancer patients. CONCLUSION: MMP11 may be a promising prognostic biomarker for pancreatic cancer patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Metaloproteinase 11 da Matriz/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Seguimentos , Humanos , Metaloproteinase 11 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/enzimologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Anticancer Res ; 39(10): 5375-5380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570432

RESUMO

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Metaloproteinase 11 da Matriz/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
3.
Int J Biochem Cell Biol ; 102: 1-9, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29890225

RESUMO

OBJECTIVE: This study aimed at finding the long non-coding RNA (lncRNA), miRNA and mRNA which played critical roles in breast cancer (BrCa) by using mixOmics R package. METHOD: The BrCa dataset were obtained from TCGA and then analyzed using "DESeq2" R package. Multivariate analyses were performed with the "mixOmics" R package and the first component of the stacked partial least-Squares discriminant analysis results were used for searching the interested lncRNA, miRNA and mRNA. qRT-PCR was applied to identify the bioinformatics results in four BrCa cell lines (MCF7, BT-20, ZR-75-1, and MX-1) and the breast epithelial cell line MCF-10 A. Then cells (MCF-1 and MX-1) were transfected with si-linc01561, miR-145-5p mimics and si-MMP11 to further investigate the effects of linc01561, miR-145-5p and MMP11 on the BrCa cells proliferation and apoptosis. RESULTS: MixOmics results showed that linc01561, miR-145-5p and MMP11 might play important roles in BrCa. qRT-PCR results identified that in BrCa cell lines, linc01561 and MMP11 were higher expressed while miR-145-5p was lower expressed compared with those in epithelial cell line. The linc01561 inhibition elevated miR-145-5p expression and then suppressed MMP11 expression. Moreover, linc01561 inhibition suppressed the BrCa cells proliferation and promoted the apoptosis, which was realized by up-regulating expression of miR-145-5p and down-regulating expression of MMP11. CONCLUSION: In summary, the findings of this study, based on ceRNA theory, combining the research foundation of miR-145-5p and MMP11, and taking linc01561 as a new study point, provide new insight into molecular-level reversing proliferation and apoptosis of BrCa.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Biologia Computacional , Progressão da Doença , MicroRNAs/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 11 da Matriz/genética
4.
Int J Med Sci ; 15(6): 653-658, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725257

RESUMO

Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer mortality worldwide. Matrix metalloproteinase-11 (MMP-11), also known as stromelysin-3, plays a critical role during tumor migration, invasion and metastasis. Here, we report on the association between five single nucleotide polymorphisms (SNPs) - rs738791, rs2267029, rs738792, rs28382575, and rs131451 - of the MMP-11 gene and HCC susceptibility, as well as clinical outcomes, in 293 patients with HCC and in 586 cancer-free controls. We found that carriers of the CT+TT allele of the rs738791 variant were at greater risk of HCC compared with wild-type (CC) carriers. Moreover, carriers of at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs738792 were likely to progress to Child-Pugh B or C grade, while individuals with at least one C allele (C/T+C/C genotype) at the MMP-11 SNP rs28382575 were at higher risk of developing stage III/IV disease, large tumors or lymph node metastasis. We believe that genetic variations in the MMP-11 gene may help to predict early-stage HCC and act as reliable biomarkers for HCC progression.


Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Metaloproteinase 11 da Matriz/genética , Adulto , Idoso , Alelos , Progressão da Doença , Feminino , Estudos de Associação Genética , Genótipo , Heterozigoto , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
5.
Proteomics ; 18(7): e1700260, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29466620

RESUMO

In the obese state, as adipose tissue expands, adipocytes become hypoxic and dysfunctional, leading to changes in the pattern of adipocyte-secreted proteins. To better understand the role of hypoxia in the mechanisms linked to obesity, we comparatively analyzed the secretome of murine differentiated 3T3-L1 adipocytes exposed to normoxia or hypoxia for 24 h. Proteins secreted into the culture media were precipitated by trichloroacetic acid and then digested with trypsin. The peptides were labeled with dimethyl labeling and analyzed by reversed phase nanoscale liquid chromatography coupled to a quadrupole Orbitrap mass spectrometer. From a total of 1508 identified proteins, 109 were differentially regulated, of which 108 were genuinely secreted. Factors significantly downregulated in hypoxic conditions included adiponectin, a known adipokine implicated in metabolic processes, as well as thrombospondin-1 and -2, and matrix metalloproteinase-11, all multifunctional proteins involved in extracellular matrix (ECM) homeostasis. Findings were validated by Western blot analysis. Expression studies of the relative genes were performed in parallel experiments in vitro, in differentiated 3T3-L1 adipocytes, and in vivo, in fat tissues from obese versus lean mice. Our observations are compatible with the concept that hypoxia may be an early trigger for both adipose cell dysfunction and ECM remodeling.


Assuntos
Adipócitos/metabolismo , Obesidade/metabolismo , Via Secretória , Células 3T3-L1 , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Animais , Hipóxia Celular , Cromatografia Líquida , Regulação da Expressão Gênica , Masculino , Espectrometria de Massas , Metaloproteinase 11 da Matriz/genética , Metaloproteinase 11 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteômica , Análise de Sequência de Proteína , Trombospondina 1/genética , Trombospondina 1/metabolismo , Trombospondinas/genética , Trombospondinas/metabolismo
6.
Anticancer Res ; 38(2): 771-778, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29374701

RESUMO

BACKGROUND/AIM: The High-Mobility Group A1 (HMGA1) protein has been implicated in human malignancies, playing an important role in cancer proliferation, angiogenesis and metastasis. Increased HMGA1 expression has been found in skin mouse tumors, whereas Hmga1-null mice were protected against skin carcinogenesis. Here, we examined the expression of HMGA1 in human skin tumors, squamous cell carcinoma and basal cell carcinoma. MATERIALS AND METHODS: Tumor and normal skin tissues from 15 affected patients were surgically excised, and mRNA and protein extraction was performed. mRNA and protein content for both HMGA1 and MMP-11, a proteinase enzyme that plays a role in tumor development and progression, was measured by real-time PCR and western blotting, respectively. Data were analyzed by the SPSS software. RESULTS: HMGA1 mRNA and protein expression patterns were higher in neoplastic skin lesions, compared to normal skin (p<0.001). Similar results were observed for MMP-11. CONCLUSION: Our data confirm previous observations in mice studies, and suggest that HMGA1 and MMP-11 may play a key role in the proliferation and progression of skin tumors in humans.


Assuntos
Proteína HMGA1a/biossíntese , Metaloproteinase 11 da Matriz/biossíntese , Neoplasias Cutâneas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteína HMGA1a/genética , Humanos , Masculino , Metaloproteinase 11 da Matriz/genética , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Cutâneas/genética
7.
Breast Cancer Res Treat ; 164(1): 41-56, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28409241

RESUMO

PURPOSE: More accurate prediction of patient outcome based on molecular subtype is required to identify patients who will benefit from specific treatments. METHODS: We selected novel 16 candidate prognostic genes, including 10 proliferation-related genes (p-genes) and 6 immune response-related genes (i-genes), from the gene list identified in our previous study. We then analyzed the association between their expression, measured by quantitative real-time reverse transcription-PCR in formalin-fixed, paraffin-embedded tissues, and clinical outcome in 819 breast cancer patients according to molecular subtype. RESULTS: The prognostic significance of clinical and gene variables varied according to the molecular subtype. Univariate analysis showed that positive lymph node status was significantly correlated with the increased risk of distant metastasis in all subtypes except the hormone receptor-negative, HER2-positive (HR-/HER2+) subtype. Most p-genes were significantly associated with poor prognosis in patients with the HR+/HER2- subtype, whereas i-genes correlated with a favorable outcome in patients with HR-/HER2+ breast cancer. In HR-/HER2+ breast cancer, four genes (three i-genes BTN3A2, CD2, and TRBC1 and the p-gene MMP11) were significantly associated with distant metastasis-free survival (DMFS). A new prognostic model for HR-/HER2+ breast cancer based on the expression of MMP11 and CD2 was developed and the DMFS for patients in the high-risk group according to our model was significantly lower than that for those in the low-risk group. Multivariate analyses revealed that our risk score is an independent prognostic factor for DMFS. Moreover, C-index showed that our risk score has a superior prognostic performance to traditional clinicopathological factors. CONCLUSIONS: Our new prognostic model for HR-/HER2+ breast cancer provides more accurate information on the risk of distant metastasis than traditional clinical prognostic factors and may be used to identify patients with a good prognosis in this aggressive subtype of breast cancer.


Assuntos
Neoplasias da Mama/genética , Antígenos CD2/genética , Metaloproteinase 11 da Matriz/genética , Prognóstico , Receptor ErbB-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Inata/genética , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade
8.
Oncotarget ; 8(15): 25289-25299, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28445974

RESUMO

Human microRNA-125a-5p (miR-125a) is expressed in most tissues where it downregulates the expression of membrane receptors or intracellular transductors of mitogenic signals, thus limiting cell proliferation. Expression of this miRNA generally increases with cell differentiation whereas it is downregulated in several types of tumors, such as breast, lung, ovarian, gastric, colon, and cervical cancers, neuroblastoma, medulloblastoma, glioblastoma, and retinoblastoma. In this study, we focused on hepatocellular carcinoma and used real-time quantitative PCR to measure miR-125a expression in 55 tumor biopsies and in matched adjacent non-tumor liver tissues. This analysis showed a downregulation of miR-125a in 80 % of patients, with a mean decrease of 4.7-fold. Comparison of miRNA downregulation with clinicopathological parameters of patients didn't yield significant correlations except for serum bilirubin. We then evaluated the expression of known targets of miR-125a and found that sirtuin-7, matrix metalloproteinase-11, and c-Raf were up-regulated in tumor tissue by 2.2-, 3-, and 1.7-fold, respectively. Overall, these data support a tumor suppressor role for miR-125a and encourage further studies aimed at the comprehension of the molecular mechanisms governing its expression, eventually leading to treatments to restore its expression in tumor cells.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Metaloproteinase 11 da Matriz/metabolismo , MicroRNAs/biossíntese , Proteínas Proto-Oncogênicas c-raf/metabolismo , Sirtuínas/metabolismo , Idoso , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/fisiologia , Regulação para Baixo , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Metaloproteinase 11 da Matriz/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Sirtuínas/genética , Transfecção , Regulação para Cima
9.
Biotechnol Appl Biochem ; 64(4): 555-563, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27302099

RESUMO

Matrix metalloproteinase-11 (MMP-11) is known to be highly expressed in metastatic and most invasive forms of tumors. Being selectively expressed in tumor tissues, MMP-11 is a promising target for immunotherapy against tumors. Here, we report the production of a thioredoxin-tagged bioactive recombinant chicken MMP-11 (cMMP-11) peptide excluding the secretory signal and propeptide in Escherichia coli T7 Express lysY using pET32b(+) vector. High-level expression and purification of the bioactive peptide were achieved by induction with 1.0 mM isopropyl-ß-d-thiogalactopyranoside for 4 H at 37 °C followed by affinity chromatography under denaturing condition and slow dialysis. The recombinant peptide exhibited both caseinolytic and gelatinase activities without requiring activation by 4-aminophenylmercuric acetate. The antisera raised against the peptide in rabbits showed a strong reaction with the whole recombinant peptide as well as 37 kDa cMMP-11 mature peptide and cross-reactivity with a 43 kDa protein in murine breast tumor of 4T1 origin in Western blot analysis. The 43 kDa protein in the tumor homogenate showed immunoreactivity with a monoclonal antibody against human MMP-11, suggesting it to be murine MMP-11 having cross-reactivity with the antisera raised against cMMP-11 peptide. Altogether, the study characterized the production of a bioactive and immunogenic recombinant cMMP-11 peptide in E. coli.


Assuntos
Escherichia coli/genética , Metaloproteinase 11 da Matriz/biossíntese , Metaloproteinase 11 da Matriz/genética , Animais , Galinhas , Clonagem Molecular , Escherichia coli/metabolismo , Metaloproteinase 11 da Matriz/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação
10.
Cancer Gene Ther ; 23(8): 258-65, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27364572

RESUMO

Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition. MiR-145 exhibited an inhibitory role in cell invasion through the post-transcriptional regulation of the novel targets MMP11 and Rab27a in TNBC cells. Additionally, miR-145 silencing could be reversed by 5-aza-2'-deoxycytidine (DAC). These results demonstrated that miR-145 has an inhibitory role in TNBC malignancy by targeting MMP11 and Rab27a, which might be potential therapeutic and diagnostic targets for TNBC.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Metaloproteinase 11 da Matriz/genética , MicroRNAs/genética , Interferência de RNA , Neoplasias de Mama Triplo Negativas/genética , Proteínas rab27 de Ligação ao GTP/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Metilação de DNA , Regulação para Baixo , Expressão Ectópica do Gene , Feminino , Humanos , Metaloproteinase 11 da Matriz/metabolismo , Regiões Promotoras Genéticas , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas rab27 de Ligação ao GTP/metabolismo
11.
Cancer Sci ; 107(9): 1233-42, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27355528

RESUMO

Our recent study of the microRNA (miRNA) expression signature of bladder cancer (BC) by deep-sequencing revealed that two miRNA, microRNA-139-5p/microRNA-139-3p were significantly downregulated in BC tissues. The aim of this study was to investigate the functional roles of these miRNA and their modulation of cancer networks in BC cells. Functional assays of BC cells were performed using transfection of mature miRNA or small interfering RNA (siRNA). Genome-wide gene expression analysis, in silico analysis and dual-luciferase reporter assays were applied to identify miRNA targets. The associations between the expression of miRNA and its targets and overall survival were estimated by the Kaplan-Meier method. Gain-of-function studies showed that miR-139-5p and miR-139-3p significantly inhibited cell migration and invasion by BC cells. The matrix metalloprotease 11 gene (MMP11) was identified as a direct target of miR-139-5p and miR-139-3p. Kaplan-Meier survival curves showed that higher expression of MMP11 predicted shorter survival of BC patients (P = 0.029). Downregulated miR-139-5p or miR-139-3p enhanced BC cell migration and invasion in BC cells. MMP11 was directly regulated by these miRNA and might be a good prognostic marker for survival of BC patients.


Assuntos
Regulação Neoplásica da Expressão Gênica , Metaloproteinase 11 da Matriz/genética , MicroRNAs/genética , Interferência de RNA , Neoplasias da Bexiga Urinária/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Genes Reporter , Humanos , Imuno-Histoquímica , Masculino , Prognóstico , RNA Mensageiro/genética , Transfecção , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
12.
Oncotarget ; 7(32): 51284-51300, 2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27323416

RESUMO

The main challenge in the treatment of prostate cancer (PCa) is that the majority of patients inevitably develop resistance to androgen deprivation. However, the mechanisms involved in hormone independent behavior of PCa remain unclear. In the present study, we identified androgen-induced miR-135a as a direct target of AR. Functional studies revealed that overexpression of miR-135a could significantly decrease cell proliferation and migration, and induce cell cycle arrest and apoptosis in PCa. We identified RBAK and MMP11 as direct targets of miR-135a in PCa by integrating bioinformatics analysis and experimental assays. Mechanistically, miR-135a repressed PCa migration through downregulating MMP11 and induced PCa cell cycle arrest and apoptosis by suppressing RBAK. Consistently, inverse correlations were also observed between the expression of miR-135a and RBAK or MMP11 in PCa samples. In addition, low miR-135a and high RBAK and MMP11 expression were positively correlated with PCa progression. Also, PI3K/AKT pathway was confirmed to be an upstream regulation signaling of miR-135a in androgen-independent cell lines. Accordingly, we reported a resistance mechanism to androgen deprivation therapy (ADT) mediated by miR-135a which might be downregulated by androgen depletion and/or PI3K/AKT hyperactivation, in castration-resistant prostate cancer (CRPC), thus promoting tumor progression. Taken together, miR-135a may represent a new diagnostic and therapeutic biomarker for castration-resistant PCa.


Assuntos
Androgênios/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Metaloproteinase 11 da Matriz/genética , MicroRNAs/genética , Neoplasias de Próstata Resistentes à Castração/genética , Proteínas Repressoras/genética , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Supressores de Tumor/efeitos dos fármacos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia
13.
Skelet Muscle ; 6: 18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27141287

RESUMO

BACKGROUND: Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. RESULTS: We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. CONCLUSIONS: These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.


Assuntos
Fibronectinas/metabolismo , Laminina/metabolismo , Metaloproteinase 11 da Matriz/metabolismo , Desenvolvimento Muscular , Músculo Esquelético/enzimologia , Tendões/enzimologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Animais Geneticamente Modificados , Regulação para Baixo , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Laminina/genética , Metaloproteinase 11 da Matriz/genética , Músculo Esquelético/embriologia , Mutação , Fenótipo , Transdução de Sinais , Tendões/embriologia , Fatores de Tempo , Técnicas de Cultura de Tecidos , Peixe-Zebra
14.
Mol Med Rep ; 13(6): 4859-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27081863

RESUMO

Osteosarcoma is one of the most common primary malignant bone cancers in juveniles and adults. Increasingly, reports indicate that microRNAs (miRNAs) may provide novel therapeutic targets for cancer treatment. The aim of the present study was to investigate the expression of miR­125a­5p and to identify its functional significance in osteosarcoma. This indicated that miR­125a­5p was downregulated in osteosarcoma tissue and cell lines using reverse transcription­quantitative polymerase chain reaction. Following transfection with miR­125a­5p mimics or the negative control, cell migration, invasion and epithelial­mesenchymal transition (EMT) assays were conducted in osteosarcoma cells. These results indicated that the overexpression of miR­125a­5p resulted in inhibited osteosarcoma cell migration, invasion and EMT in vitro. Furthermore, mechanistic studies showed that matrix metallopeptidase­11 (MMP­11), was a direct target of miR­125a­5p in osteosarcoma. Taken together, the data demonstrate that miR­125a­5p functions as a tumor suppressor gene and serves an important role in inhibiting osteosarcoma cell migration, invasion and EMT by targeting MMP­11.


Assuntos
Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Metaloproteinase 11 da Matriz/genética , MicroRNAs/genética , Osteossarcoma/genética , Interferência de RNA , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Humanos , Osteossarcoma/patologia
15.
Mol Carcinog ; 55(11): 1489-1502, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26349857

RESUMO

The biological heterogeneity of breast cancer leads to the need for finding new approaches to understand the mechanisms implicated in breast cancer progression. The tumor stroma appears as a key in the progression of solid tumors towards a malignant phenotype. Cancer associated fibroblasts (CAFs) may orchestrate a functional "corrupted" stroma which in turn helps metastatic spread. In this study, we investigated by real-time PCR, the expression of 19 factors by normal breast-associated fibroblasts (NAFs) and CAFs, which were implicated in several actions promoting tumor growth, such as extracellular matrix remodeling, inflammation and invasion. Also, we explored the influence of inflammatory cells phenotypes (MMP11 status) and breast cancer cell lines (MCF-7 and MDA-MB-231) on the molecular profile of CAFs. If we consider that one of the major sources of CAFs are resident NAFs, the transition of NAFs into CAFs is associated with molecular changes involving the overexpression of some molecular factors of biological importance in tumor progression. In addition, the characterization of the tumor stroma regarding to the MMP11 status by MICs reflects a type of fibroblasts which contribute even more to tumor progression. Moreover, different patterns in the induction of the expression of factors by CAFs were observed, depending on the tumor cell line which they were co-cultured with. Furthermore, CAFs influence TGFß expression in both cancer cell lines. Therefore, this study can help to a better characterization of tumor stroma in order to improve the prognostic evaluation, as well as to define the different populations of CAFs as potential therapeutic targets in breast cancer. © 2015 Wiley Periodicals, Inc.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Fibroblastos/imunologia , Perfilação da Expressão Gênica/métodos , Metaloproteinase 11 da Matriz/genética , Fator de Crescimento Transformador beta/genética , Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/citologia , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Progressão da Doença , Feminino , Fibroblastos/citologia , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Metaloproteinase 11 da Matriz/metabolismo , Fenótipo , Estudos Prospectivos , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral
16.
J Transl Med ; 13: 337, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26507719

RESUMO

BACKGROUND: This study aimed to investigate the expression of CD147 and MMP-11 in human colorectal cancer (CRC) and to evaluate their clinical significance. METHODS: Real-time polymerase chain reaction was used to evaluate CD147 and MMP-11 mRNA level in 56 pairs of fresh CRC samples matched with adjacent normal mucosa. The protein expression of CD147 and MMP-11 in CRC specimens and corresponding normal colorectal mucosa were evaluated by immunohistochemistry on CRC tissue microarrays. Expression and co-localization of these two proteins in human colorectal cancer tissue were also evaluated by laser scanning confocal microscopy. Furthermore, their correlations with clinicopathological factors and overall survival after surgery were evaluated. RESULTS: Both CD147 and MMP-11 were demonstrated to be over-expressed at mRNA level (P < 0.001, both) and protein level (P < 0.001, both) in CRC tissue than paired normal mucosa. Spearman rank test showed a positive correlation between these two proteins (P = 0.025). Immunofluorescence double staining confirmed the co-localization of CD147 and MMP-11 in paraffin-embedded tissues of CRC patients. Expression of CD147 and MMP-11 were both correlated with CRC lymph node metastasis (P = 0.021 and P = 0.031, respectively), distant metastasis (P < 0.001 and P = 0.013, respectively) and TNM stage (P = 0.006 and P = 0.049, respectively). Univariate survival analysis showed that both CD147 and MMP11 expression was significantly associated with shorter survival time (P = 0.001 and P = 0.009, respectively). Additionally, in multivariate analysis, both CD147 and MMP-11 were proved to be independent prognostic factors (P = 0.009, 0.028, respectively). CONCLUSIONS: These results indicated that both CD147 and MMP-11 may be involved in the progression of colorectal cancer, and they are potential prognostic factors and might become new therapeutic targets for CRC patients.


Assuntos
Basigina/genética , Neoplasias Colorretais/patologia , Metaloproteinase 11 da Matriz/genética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética
17.
BMC Cancer ; 15: 473, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26084486

RESUMO

BACKGROUND: In order to identify biomarkers involved in breast cancer, gene expression profiling was conducted using human breast cancer tissues. METHODS: Total RNAs were extracted from 150 clinical patient tissues covering three breast cancer subtypes (Luminal A, Luminal B, and Triple negative) as well as normal tissues. The expression profiles of a total of 50,739 genes were established from a training set of 32 samples using the Agilent Sure Print G3 Human Gene Expression Microarray technology. Data were analyzed using Agilent Gene Spring GX 12.6 software. The expression of several genes was validated using real-time RT-qPCR. RESULTS: Data analysis with Agilent GeneSpring GX 12.6 software showed distinct expression patterns between cancer and normal tissue samples. A group of 28 promising genes were identified with ≥ 10-fold changes of expression level and p-values < 0.05. In particular, MMP11 and HPSE2 were closely examined due to the important roles they play in cancer cell growth and migration. Real-time RT-qPCR analyses of both training and testing sets validated the gene expression profiles of MMP11 and HPSE2. CONCLUSIONS: Our findings identified these 2 genes as a novel breast cancer biomarker gene set, which may facilitate the diagnosis and treatment in breast cancer clinical therapies.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica , Glucuronidase/genética , Metaloproteinase 11 da Matriz/genética , Transcriptoma , Biomarcadores Tumorais , Análise por Conglomerados , Biologia Computacional , Bases de Dados de Ácidos Nucleicos , Feminino , Humanos , Reprodutibilidade dos Testes
18.
Head Neck ; 37(10): 1425-31, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24838924

RESUMO

BACKGROUND: The purpose of this study was to investigate the influence of genetic polymorphisms of the matrix metalloproteinase-11 (MMP-11) gene on the susceptibility of oral squamous cell carcinoma (OSCC). METHODS: Four single-nucleotide polymorphisms (SNPs) of the MMP-11 gene from 595 patients with oral cancer and 561 noncancer controls were analyzed by real-time polymerase chain reaction (PCR). RESULTS: MMP-11 gene polymorphisms exhibit synergistic effects of environmental factors (betel nut chewing and tobacco use) on the susceptibility of OSCC. Furthermore, among patients with OSCC with betel nut consumption, those who have at least one polymorphic C allele of MMP-11 rs738792 have an increased incidence of lymph node metastasis when compared with those patients homozygous for T/T. CONCLUSION: Our results showed that the combined effects of the MMP-11 gene polymorphisms and environmental carcinogens are related to an increased risk for the development of OSCC and may be a predictive factor for tumor lymph node metastasis in Taiwanese with OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Metaloproteinase 11 da Matriz/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco
19.
PLoS One ; 9(11): e113129, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25423087

RESUMO

BACKGROUND: Matrix metalloproteinase-11 (MMP-11) is reported to be overexpressed in several cancers and may contribute to tumorigenesis. The current study investigated the association between the clinicopathological characteristics and plasma level of MMP-11 in oral squamous cell carcinoma (OSCC) patients. METHODOLOGY AND PRINCIPAL FINDINGS: The plasma MMP-11 concentration was determined by ELISA on 330 male OSCC patients. In addition, the metastatic effects of the MMP-11 knockdown on the oral cancer cells were investigated by cell migration assay. Our results showed that the plasma MMP-11 levels were significantly higher in patients with advanced T status (p = 0.001), lymph node metastasis (p = 0.006) and higher TNM stages (p<0.001). Moreover, treatment with the MMP-11 shRNA exerted an inhibitory effect on migration in SCC9 oral cancer cells. CONCLUSION: Our study showed that plasma level of MMP-11 may be useful for assessment of the disease progression, especially lymph node metastasis, in patients with OSCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/enzimologia , Metaloproteinase 11 da Matriz/sangue , Neoplasias Bucais/enzimologia , Adulto , Western Blotting , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Técnicas de Silenciamento de Genes , Humanos , Masculino , Metaloproteinase 11 da Matriz/genética , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Reação em Cadeia da Polimerase em Tempo Real
20.
Cancer Med ; 3(5): 1197-210, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25081520

RESUMO

MMP-11 is a key factor in physiopathological tissue remodeling. As an active form is secreted, its activity must be tightly regulated to avoid detrimental effects. Although TIMP-1 and TIMP-2 reversibly inhibit MMP-11, another more drastic scenario, presumably via hydrolysis, could be hypothesized. In this context, we have investigated the possible implication of MMP-14, since it exhibits a spatiotemporal localization similar to MMP-11. Using native HFL1-produced MMP-11 and HT-1080-produced MMP-14 as well as recombinant proteins, we show that MMP-11 is a MMP-14 substrate. MMP-14 cleaves MMP-11 catalytic domain at the PGG(P1)-I(P1')LA and V/IQH(P1)-L(P1')YG scissile bonds, two new cleavage sites. Interestingly, a functional test showed a dramatical reduction in MMP-11 enzymatic activity when incubated with active MMP-14, whereas inactive point-mutated MMP-14 had no effect. This function is conserved between human and mouse. Thus, in addition to the canonical reversible TIMP-dependent inhibitory system, irreversible MMP proteolytic inactivation might occur by cleavage of the catalytic domain in a MMP-dependent manner. Since MMP-14 is produced by HT-1080 cancer cells, whereas MMP-11 is secreted by HFL1 stromal cells, our findings support the emerging importance of tumor-stroma interaction/cross-talk. Moreover, they highlight a Janus-faced MMP-14 function in the MMP cascade, favoring activation of several pro-MMPs, but limiting MMP-11 activity. Finally, both MMPs are active at the cell periphery. Since MMP-14 is present at the cell membrane, whereas MMP-11 is soluble into the cellular microenvironment, this MMP-14 function might represent one critical regulatory mechanism to control the extent of pericellular MMP-11 bioavailability and protect cells from excessive/inappropriate MMP-11 function.


Assuntos
Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Sequência de Aminoácidos , Animais , Domínio Catalítico , Linhagem Celular Tumoral , Ativação Enzimática , Expressão Gênica , Humanos , Metaloproteinase 11 da Matriz/química , Metaloproteinase 11 da Matriz/genética , Metaloproteinase 14 da Matriz/química , Metaloproteinase 14 da Matriz/genética , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Conformação Proteica , Proteólise , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA