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1.
Anticancer Res ; 40(1): 67-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892553

RESUMO

BACKGROUND/AIM: Aberrant expression of the SEI1 oncogene has been prevalently found in a variety of human cancers, including oral squamous cell carcinoma (OSCC). Recent studies have shown that cisplatin up-regulates the expression of SEI1 in breast and bladder cancer cells, thus inhibiting apoptosis and cell death in these cells. In the present study, we investigated the impact of cisplatin on the expression of SEI1 in OSCC cells. MATERIALS AND METHODS: Four OSCC cell lines, CAL27, SCC4, SCC15, and SCC22A were treated with cisplatin and 5-fluorouracil, and changes in SEI1 expression in these cells were evaluated using quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analyses. RESULTS: Cisplatin significantly induced SEI1 expression in the tested OSCC cells. Contrarily, cisplatin treatment did not affect the expression of gankyrin and BMI1, two oncogenes frequently overexpressed in a coordinate manner with SEI1 in OSCC. Additionally, 5-fluorouracil did not bring about any detectable changes in SEI1 expression in these cells. CONCLUSION: Cisplatin-induced up-regulation of SEI1 expression in OSCC is specific, and such induction could underlie the development of resistance to cisplatin in OSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Bucais/genética , Oncogenes , Fatores de Transcrição/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , Humanos
2.
BMC Oral Health ; 20(1): 24, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996191

RESUMO

BACKGROUND: Our study aimed to reveal the regulatory mechanisms of miRNAs and matrix metalloproteinases (MMPs) in oral squamous cell carcinoma (OSCC). METHODS: The mRNA and miRNA expression profiles of six metastatic tumour samples, six nonmetastatic tumour samples, and six normal tissue samples were used for microarray analysis. Moreover, the important genes and miRNAs were validated by published profiles in Oncomine and by qRT-PCR. RESULTS: MMP7, MMP13, and MMP10 were upregulated, and MMP12 and MMP9 were downregulated in metastatic tumours compared with nonmetastatic tumours. MMP7 was regulated by miR-4697-5p and miR-7109-5p. MMP7 and MMP13 were upregulated in OSCC samples compared with normal samples in Oncomine. Moreover, qRT-PCR revealed that the expression of miR-7109-5p and miR-34b was decreased in metastatic tumours compared with nonmetastatic tumours. CONCLUSIONS: Our study suggested that miR-7109-5p and miR-34b might play important roles in the metastasis of OSCC by regulating MMP7 and MMP13 expression, respectively.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Metaloproteinases da Matriz/metabolismo , MicroRNAs/genética , Análise em Microsséries/métodos , Neoplasias Bucais/genética , Metástase Neoplásica/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , RNA Neoplásico/sangue , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genética
3.
J Oral Pathol Med ; 49(1): 21-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31397491

RESUMO

BACKGROUND: Increasing evidence suggests that dysregulated long non-coding RNAs (lncRNAs) are involved in tumorigenesis and progression. RP11-284F21.9, one of the temporally expressed S-phase lncRNAs in cancer cells, was recently identified by nascent RNA capture sequencing. METHODS: Cal-27, Tca8113, SCC-9, HB56, and oral squamous cell carcinoma (OSCC) tissues were used in the experiment. RNA extraction, qRT-PCR, plasmid construction, cell proliferation, EdU labeling, Transwell migration, luciferase reporter, and western blotting were used to investigate the exact role and function of RP11-284F21.9 in cancer. RESULTS: RP11-284F21.9 was upregulated in human OSCC samples and cell lines. RP11-284F21.9 depletion suppressed the proliferation, migration, and invasion of OSCC cell lines. There was interaction between RP11-284F21.9, miR-383-5p, and MAL2. Increased MAL2 and decreased miR-383-5p expression were also detected in OSCC tissues and cell lines. In addition, RP11-284F21.9 knockdown could reduce MAL2 expression, while miR-383-5p inhibitors abolished this repressive effect. RP11-284F21.9 acted as a competing endogenous RNA (ceRNA) of miR-383-5p, leading to MAL2 upregulation, and subsequently promoted OSCC progression. CONCLUSION: RP11-284F21.9/miR-383-5p represents a novel and potential therapeutic target for the treatment of OSCC.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs/genética , Neoplasias Bucais , Proteínas Proteolipídicas Associadas a Linfócitos e Mielina/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética
4.
Oral Dis ; 26(1): 53-61, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605415

RESUMO

OBJECTIVE: Proteasome activator 28γ (PA28γ) upregulation plays a critical role in the carcinogenesis of many malignancies, including oral cancer. We aim to screen the related genes of PA28γ and investigate their function in oral mucosa carcinogenesis. MATERIALS AND METHODS: Bioinformatics analysis was performed to screen the related genes of PA28γ. Immunohistochemical analysis was carried out to validate their correlation in oral squamous cell carcinoma (OSCC) and detect their expression levels in the whole process of oral mucosa carcinogenesis. The Kaplan-Meier method was used for estimating the overall survival, and the Cox models were constructed to predict the prognosis. RESULTS: U2 small nuclear RNA auxiliary factor 1 (U2AF1) was screened out, and the correlation between U2AF1 and PA28γ was further validated in OSCC. The expression levels of PA28γ and U2AF1 were gradually increased from normal to oral potentially malignant disorders (OPMD) to OSCC tissues. Overall survival was significantly shorter in patients with high U2AF1 expression and the combined application of U2AF1 and PA28γ notably improved the accuracy of prognosis prediction. CONCLUSION: U2AF1 and PA28γ might play pivotal roles in the progression of OPMD, which may provide insights into the development of new therapeutic strategies to prevent OPMD from becoming malignant.


Assuntos
Autoantígenos/genética , Carcinogênese , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Complexo de Endopeptidases do Proteassoma/genética , Fator de Processamento U2AF/genética , Animais , Linhagem Celular Tumoral , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos C57BL , Mucosa Bucal
5.
Oral Dis ; 26(1): 62-71, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31618798

RESUMO

BACKGROUND: Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS: The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS: The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION: The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Proteínas Ligadas por GPI/genética , Neoplasias Bucais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Invasividade Neoplásica , Prognóstico
6.
Odontology ; 108(1): 91-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31062130

RESUMO

Several growth factors and their receptors, such as epidermal growth factor receptor, have been studied as prognostic biomarkers for many epithelial malignancies. The signal transduction cascade of those receptors includes RAS/RAF/ERK, PI3K/Akt/mTOR, and STAT3 pathways. The aim of this study was to investigate the expression levels of several key proteins of those pathways in patients with oral squamous cell carcinoma (OSCC) and oral epithelial precursor lesions (OEPLs), and to correlate the expressions of these proteins with clinicopathologic features and prognosis. Fifteen leukoplakia (LP), 15 low-grade epithelial dysplasia, 15 high-grade epithelial dysplasia (HD), and 132 OSCC specimens were immunohistochemically examined for KRAS, HRAS, NRAS, BRAF, pERK1/2, pAkt, pmTOR, and pSTAT3 expression. Immunoreactivity for these molecules predominantly occurred in regions OEPL basal to prickle layers and in most OSCC cells. KRAS and NRAS expression was significantly lower in OSCC than in OEPLs, while pAkt and pmTOR showed higher expression in OSCC than in OEPLs. pERK1/2 expression was significantly higher in HD than in LP. In OSCC, KRAS and NRAS immunoreactivity was significantly higher in advanced age and male gender. In addition, higher immunoreactivity was shown in pERK1/2 in female gender and advanced TNM stage, pAkt in advanced T classification and cases without postoperative metastasis, pmTOR in advanced mode of invasion, and pSTAT3 in invasion depth. Correlations between these markers and clinicopathological variables were also noted. MAPK, Akt, and STAT3 pathways might play diverse roles in oral carcinogenesis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Masculino , Neoplasias Bucais/genética , Transdução de Sinais
7.
Anticancer Res ; 39(12): 6515-6521, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810916

RESUMO

BACKGROUND/AIM: Oral cancer is of the highest incidence worldwide in Taiwan, and a better marker for personalized therapeutic strategies such as immunotherapies is urgently needed. Interleukin-12 (IL12) is a cytokine that has been reported to exhibit potent tumoricidal effects, however, its genotypic contribution to oral cancer is still largely unknown. The current study aimed at investigating whether IL12B rs3212227 genotype is associated with oral cancer in Taiwan. MATERIALS AND METHODS: Genotypic characteristics of IL12B rs3212227 were determined among 958 oral cancer cases and age- and gender-matched individuals via typical polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: The AA, AC and CC genotypes of IL12B rs3212227 were 38.2, 38.9 and 22.9% in the case group and 36.2, 41.5 and 22.3% in the control group (p=0.5189), respectively. CONCLUSION: IL12B rs3212227 genotype was associated with oral cancer risk only in betel quid chewers.


Assuntos
Areca/efeitos adversos , Subunidade p40 da Interleucina-12/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Taiwan
8.
Hum Genet ; 138(11-12): 1379-1389, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31679052

RESUMO

Betel quid (BQ) chewing is a prevailing risk for oral squamous cell carcinoma (OSCC) in Southeast Asia. Yet, the detailed mechanisms by which BQ chewing damages the genome are still not fully understood. Through exome sequencing of tumor-normal pairs from 196 male patients with OSCC, including 95 habitual BQ chewers and 101 non-BQ users, we conducted a quantitative survey of mutational signatures and genomic aberrations and explored their association with BQ chewing. We found that BQ-associated elevation in mutation rate was seen in cancers of the tongue, but not in overall OSCC. Additionally, we identified a mutational signature that is enriched in tumors from BQ users. Moreover, the numbers of small insertions and deletions (INDELs) and breakpoints derived from structural variations (SV) were increased, whereas the extent of loss of heterozygosity was decreased in BQ-related OSCC genomes. However, neither the number of base substitutions and microsatellite instability events nor the extent of copy-number alterations differed between BQ-related and -unrelated OSCC. In conclusion, consistent with the proposition that BQ chewing increases OSCC risk as a mutagen, our results unveil a BQ-associated mutational signature and indicate mutagenic impacts of BQ chewing on preferentially eliciting INDELs and SV-related breakpoints in OSCC genomes.


Assuntos
Areca/efeitos adversos , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mastigação , Neoplasias Bucais/genética , Mutação , Adulto , Idoso , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/epidemiologia
9.
Anticancer Res ; 39(10): 5623-5630, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570459

RESUMO

BACKGROUND: This study aimed to investigate p16 and COX2 expression in oropharyngeal squamous cell carcinoma (OPSCC), and evaluate the prognostic role of COX2 expression under the new TNM classification. MATERIALS AND METHODS: Biopsy specimens obtained from 75 patients with OPSCC were stained for p16 and COX2 expression immunohistochemically. The results and clinical records were analyzed retrospectively. RESULTS: Fifty-nine patients (79%) were positive for p16. COX2 expression was correlated with poor relapse-free survival in patients overall, and in p16-positive patients. Smoking was positively associated with COX2 expression. Moreover, both positive COX2 expression and anterior wall tumor subsite were independently correlated with lymph node metastasis, which was the only independent prognostic factor in p16-positive OPSCC. CONCLUSION: The p16-positive rate in this study was comparable with that in the USA and Europe, and higher than that in other Asian countries. COX2 expression might affect the prognosis of p16-positive OPSCC through promoting lymph node metastasis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor p16 de Quinase Dependente de Ciclina/genética , Ciclo-Oxigenase 2/genética , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Arch Oral Biol ; 108: 104547, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525531

RESUMO

OBJECTIVE: This study investigated the risk and prognostic value of single nucleotide polymorphisms (SNP) inIL-8, MMP-1 and MMP-13 in oral and oropharyngeal squamous cell carcinomas (SCCs). DESIGN: SNPs rs2227532 and rs4073 inIL-8, rs2071230 and rs470558 in MMP-1, and rs2252070 in MMP-13 were genotyped in 125 oral and oropharyngeal SCC patients and 130 healthy controls, using TaqMan allelic discrimination assays. Multiple logistic regression models were used to explore the association between SNPs and cancer development, as well as SNP-SNP interaction and gene-environmental factor (GxE) interaction. Univariate and multivariate methods were applied for survival analyses. RESULTS: With exception of rs2227532, all the SNPs were in Hardy-Weinberg equilibrium in the control. No associations between rs4073 in IL-8 and rs2071230 and rs470558 in MMP-1 were observed, but rs2252070 in MMP-13, in the dominant model, was associated in a protective manner to oral and oropharyngeal SCC (OR: 0.20, 95% CI: 0.06-0.71, p = 0.007). All SNPs interact significantly with cigarette smoking and alcohol consumption on susceptibility to oral and oropharyngeal SCC, but they showed no influence on survival of the patients. CONCLUSIONS: Our results show that rs2252070 inMMP-13 may confer protection effect against oral and oropharyngeal SCC. In addition, the combined effects of IL-8 (rs4073), MMP-1 (rs2071230 and rs470558) and MMP-13 (rs2252070) with environmental carcinogens, such as tobacco and alcohol, are related to increased risk for oral and oropharyngeal SCC development.


Assuntos
Carcinoma de Células Escamosas , Interleucina-8 , Metaloproteinase 13 da Matriz , Metaloproteinase 1 da Matriz , Neoplasias Bucais , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Humanos , Interleucina-8/genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 13 da Matriz/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Prognóstico
11.
Shanghai Kou Qiang Yi Xue ; 28(3): 225-230, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489406

RESUMO

PURPOSE: To investigate the mechanism of ANXA1 in TPF chemotherapy of oral squamous cell carcinoma (OSCC). METHODS: ANXA1 overexpression and low-expression cell lines were constructed. The role of ANXA1 in TPF chemotherapy was analyzed by cell proliferation, cytotoxicity test, real-time PCR and Western blot, and the mechanism of ANXA1 in TPF chemotherapy through EMT (epithelial-mesenchymal transition) pathway was discussed. The data were analyzed with SPSS 18.0 software package. RESULTS: After overexpression of ANXA1, cell growth rate decreased, cell cycle slowed down, sensitivity to TPF-induced drugs decreased, and EMT occurred in OSCC. After underexpression of ANXA1, cell growth rate increased, cell cycle accelerated, sensitivity to TPF chemotherapeutic drugs increased, and reverse EMT occurred in OSCC. CONCLUSIONS: In TPF chemotherapy of OSCC, overexpression of ANXA1 results in EMT of cells, which leads to decreased chemosensitivity.


Assuntos
Anexina A1 , Antineoplásicos , Carcinoma de Células Escamosas , Transição Epitelial-Mesenquimal , Neoplasias Bucais , Anexina A1/metabolismo , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética
12.
Cell Biochem Funct ; 37(8): 572-577, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31502267

RESUMO

Among the types of cancers that may occur in the oral cavity, squamous cell carcinomas (SCC) of the mouth have a higher incidence and are associated with increased rates of morbidity and mortality. Among steps from the beginning to the progression of the tumour, DNA Repair System is highlighted. The present study aims to conduct a systematic review of the literature on the expression of the repair genes hMSH2 and hMSH6 in patients with SCC in the mouth and oropharyngeal region. The search was performed in databases such as PubMed, Lilacs, and Scielo and included articles published in English from 1999 until 2015. The search in the above-mentioned databases initially yielded 15 scientific articles related to the proposed objective. After a detailed analysis of each of them, only 8 were included in the present review, precisely because they met the inclusion criteria determined in the method. All the reviewed works were unanimous in recognizing the veracity and complexity of the Genomic Repair System, also called Mismatch Repair System, confirming the participation of repair gene proteins (such as hMSH2 and hMSH6) in patients with oral cancer and even of lesions that are susceptible to malignization. SIGNIFICANCE OF THE STUDY: Worldwide, there are an estimated 300 thousand new cases of oral cancer per year. Studies have shown a greater risk in individuals who are smokers and alcohol consumers in developing mouth cancer. Many steps are observed from the beginning to the progression of the tumour, highlighted among them is the moment in which genetic, and epigenetic alterations will interfere in the functioning of the DNA Repair System. This work presents a survey of current knowledge about the involvement of repair genes, especially those of the MutSα system, in the development and progression of oral cancer.


Assuntos
Carcinoma de Células Escamosas/patologia , Reparo do DNA/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , Bases de Dados Factuais , Humanos , Neoplasias Bucais/genética , Proteína 2 Homóloga a MutS/genética
13.
Ann Clin Lab Sci ; 49(4): 457-467, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31471334

RESUMO

This study aims to explore the regulatory mechanism of hypoxia-inducible factor HIF-1α on Kv3.4. Oral squamous cell carcinoma (OSCC) cell lines SCC3 and CAL27 were used in this study. Western blotting and qRT-PCR methods were used to detect Kv3.4 expression levels in OSCC and their adjacent tissues. The expression changes of Kv3.4 and HIF-1α in a hypoxic environment were detected in cell lines. The stable OSCC cell lines with knockouts of HIF-1α and Kv3.4 were constructed. Transwell and CCK-8 assays were used to detect changes in the invasion, migration and proliferation ability after transfection. Chromatin immunoprecipitation and luciferase reporter gene assays were used to determine the regulatory and binding sites of HIF-1α on Kv3.4. The expression level of Kv3.4 in oral cancer tissue was higher than normal oral epithelium's regular value. The expression level of HIF-1α and Kv3.4 increased under hypoxia. Knocking out HIF-1α and Kv3.4 could reduce the invasion, migration and proliferation of cells. A down regulation of HIF-1α will reduce the Kv3.4 expression level. Overexpressing Kv3.4 after knocking down HIF-1α partially restored the proliferation and invasion of cell lines. Therefore, HIF-1α regulates the invasion, migration and proliferation of oral cancer cells by regulating Kv3.4 expression.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Bucais/patologia , Canais de Potássio Shaw/metabolismo , Sequência de Bases , Hipóxia Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Bucais/genética , Invasividade Neoplásica , Regiões Promotoras Genéticas/genética , Ligação Proteica , Canais de Potássio Shaw/genética
14.
Artif Cells Nanomed Biotechnol ; 47(1): 3278-3285, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31379206

RESUMO

Objective: The current study aimed to explore the function of miR-638 on the progression of oral squamous cell carcinoma (OSCC) and relevant molecular mechanisms. Methods: Expression profile of miR-638 in OSCC tissues and cells was detected using quantitative real-time polymerase chain reaction (qRT-PCR) method. Chi-square test was performed to estimate the relationship between miR-638 and clinical parameters of OSCC cases. Cell viability and motility abilities were estimated using MTT and transwell assays, respectively. Potential targets of miR-638 in OSCC were identified through bioinformatics analysis and luciferase reporter assay. Results: MiR-638 exhibited decreased expression in OSCC tissues and cells, compared to non-cancerous controls (P < .05 for both). Moreover, its down-regulation was closely correlated with lymph node metastasis (P = .044) and TNM stages (P = .001). Enforced miR-638 expression reduced cell proliferation, migration and invasion, while its knockdown exhibited opposite effects. Phospholipase D1 (PLD1) was confirmed as a target of miR-638 in OSCC. MiR-638 could inhibit wnt/ß-catenin pathway through targeting PLD1, thus realizing its anti-tumour action in OSCC. Conclusion: MiR-638 may be a tumour suppressor in OSCC by targeting PLD1/Wnt/ß-catenin pathway.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Fosfolipase D/genética , Via de Sinalização Wnt/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética
15.
Anticancer Res ; 39(8): 4285-4289, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366519

RESUMO

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a cancer with poor prognosis due to therapy resistance, locoregional recurrences, and distant metastases. There is on increased interest in profiling the androgen receptor (AR) in cancer biology. The aim of this study was to compare AR and Ki-67 levels in the neoplastic epithelium and stroma between non-metastatic and metastatic stages of OSCC. PATIENTS AND METHODS: Tissue specimens of 101 non-metastatic and 95 metastatic OSCC patients were analyzed by immunohistochemistry. RESULTS: More than 20% of AR-positive cytoplasmic staining of OSCC epithelium was significantly associated with nuclear AR levels in the epithelium and increased AR levels in the stroma. In metastatic OSCC patients, Ki-67 was significantly higher than in non-metastatic OSCC patients. CONCLUSION: More than 20% of AR-positive cytoplasmic staining in neoplastic OSSC epithelium is a significant predictor of OSCC progression risk.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Antígeno Ki-67/genética , Neoplasias Bucais/genética , Receptores Androgênicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fatores de Risco
16.
Gene ; 716: 144033, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377313

RESUMO

Oral squamous cell cancer (OSCC) is one of the causes of death worldwide. The purpose of this project was to define the restoring of microRNA-143 in HN-5 cells and discover molecular apparatuses responsible for the anticancer processes. Firstly, expression levels of miR-143, K-Ras, MMP9 and C-Myc were evaluated in OSCC tissues. Then, microRNA-143 was transfected into HN-5 cells. The cytotoxic effects of microRNA-143 on HN-5 cells were evaluated. To estimate the effects of microRNA-143 on cell migration, wound healing assay was done. The expression levels of microRNA-143, K-Ras, MMP9, C-Myc, ADAMTS and CXCR4 were evaluated via the qRT-PCR method. microRNA-143 mimic inhibited cell migration in HN-5 cell line. microRNA-143 mimic decreased K-Ras, MMP9, C-My, ADAMTS and CXCR4 gene expression. microRNA-143 can inhibit HN-5 cells migration in vitro by down-regulating the expression of invasion-linked genes. Hence, microRNA-143 can be a new diagnostic biomarker and new therapeutic target for OSCC.


Assuntos
MicroRNAs/metabolismo , Neoplasias Bucais/genética , Neoplasias de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Metástase Neoplásica , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transfecção
17.
Oncol Rep ; 42(4): 1319-1328, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364748

RESUMO

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer­associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR­382­5p in this process was elucidated. In this study, according to the α­SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs­rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co­cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR­382­5p. Western blot analysis was used to measure the expression of migration and invasion­associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR­382­5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR­382­5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF­derived exosomes transported miR­382­5p to OSCC cells. The present study confirmed a new mechanism of CAF­facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.


Assuntos
Fibroblastos Associados a Câncer/patologia , Exossomos/genética , MicroRNAs/biossíntese , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Actinas/biossíntese , Adulto , Idoso , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Exossomos/metabolismo , Exossomos/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Metástase Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
18.
Oral Dis ; 25(7): 1707-1714, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295753

RESUMO

OBJECTIVES: To identify molecular characteristics of keratosis of unknown significance and to nominate pathways of molecular progression to oral cancer. Our work could provide a rationale for monitoring and treating these lesions definitively. METHODS: Patients with oral leukoplakia were eligible for our prospective observational study. We correlated alterations in cancer-associated genes with clinical and histopathologic variables (keratosis of unknown significance vs. moderate-to-severe dysplasia) and compared these alterations to a previously molecularly characterized oral cancer population. RESULTS: Of 20 enrolled patients, 13 (65%) had evidence of keratosis of unknown significance, while seven (35%) had dysplasia. Nine patients (45%) developed oral cancer (4/13 with keratosis of unknown significance, 5/7 with dysplasia). At a median follow-up of 67 (range 22-144) months, median overall survival was significantly shorter for patients with dysplasia (hazard ratio 0.11, p = .02). KMT2C and TP53 alterations were most frequent (75% and 35%, respectively). There were molecular similarities between keratosis of unknown significance and dysplasia patients, with no significant differences in mutational frequency among genes with ≥15% rate of alteration. CONCLUSIONS: Among patients with leukoplakia, both patients with keratosis of unknown significance and patients with dysplasia developed oral cancer. Molecular alterations between these two groups were similar at this sample size.


Assuntos
Ceratose/epidemiologia , Leucoplasia Oral/etiologia , Neoplasias Bucais/genética , Lesões Pré-Cancerosas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genômica , Humanos , Ceratose/patologia , Leucoplasia Oral/epidemiologia , Leucoplasia Oral/genética , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/epidemiologia , Lesões Pré-Cancerosas/patologia , Estudos Prospectivos
19.
Oral Dis ; 25(7): 1715-1723, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295760

RESUMO

OBJECTIVE: The molecular mechanisms underlying the development of dysplasia in leukoplakia are unknown. We used RNA sequencing to examine the molecular and biological pathway differences in oral leukoplakia with and without oral epithelial dysplasia. MATERIALS AND METHODS: Excisional biopsy specimens (25) were taken from 24 patients with oral leukoplakia diagnosed histopathologically as either oral epithelial dysplasia (13) or epithelial hyperplasia and keratosis without dysplasia (12). Transcriptome analysis used RNA sequencing, differential expression and hierarchical clustering. Biological signalling was examined by gene ontology, pathway and protein-protein interaction analysis. RESULTS: Differential expression analysis showed distinction between the two groups identifying 47 genes as altered in leukoplakia with dysplasia, including SAA1, SAA2, KRT31, KRT37, KRT76, ROBO2, DNAJB5 and DNAJA4. Using hierarchical clustering, dysplastic leukoplakia readily segregated from leukoplakia without dysplasia. Pathway and ontology enrichment analysis provided evidence that downregulation of extracellular matrix (ECM) pathways was a feature of dysplastic lesions. CONCLUSION: Our results suggest that there are detectable changes in the molecular profile of oral leukoplakia exhibiting dysplasia including downregulated ECM as a distinguishing feature of dysplastic lesions. This suggests that reactive changes in stroma may be an early manifestation of dysplastic development. Our study also demonstrates the feasibility of detecting such molecular changes in oral leukoplakia, providing avenues for further investigation of molecular mechanisms of oral dysplasia.


Assuntos
Carcinoma in Situ/patologia , Hiperplasia/patologia , Ceratose/patologia , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma in Situ/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Hiperplasia/genética , Ceratose/genética , Leucoplasia Oral/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Análise de Sequência de RNA
20.
J Oral Pathol Med ; 48(10): 911-918, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31323152

RESUMO

BACKGROUND: Oral squamous cell carcinoma is the eighth most common cancer worldwide with a relatively high rate of metastasis (~40%). Previously, we showed that microRNA-138 serves as a functional tumor suppressor and plays an important role in oral squamous cell carcinoma metastasis. However, to date, microRNA-138 expression has not been examined in this tumor tissue. Herein, we demonstrated that microRNA-138 expression is downregulated in metastatic oral squamous cell carcinoma specimens using tissue microarray technology with in situ hybridization. METHODS: The study included 254 oral squamous cell carcinoma patients from two centers (160 from the Chengdu center and 90 from the Guangzhou center) and four healthy volunteers. RESULTS: Multivariate analysis showed that microRNA-138 expression was independent of tumor stage, age, gender, smoking, and alcohol consumption in oral squamous cell carcinoma patients. Interestingly, patients that expressed lower levels of microRNA-138 (determined by in situ hybridization) were more prone to regional lymph node metastasis and exhibited poorer outcomes. These findings support the role of microRNA-138 as a tumor suppressor in oral squamous cell carcinoma. CONCLUSION: In summary, the expression level of microRNA-138 is negatively correlated with oral squamous cell carcinoma metastasis; the lower the expression of microRNA-138, the higher the rate of metastasis and the poorer the prognosis of the patients. Therefore, our study confirms that microRNA-138 serves as a tumor suppressor and plays a functional role in oral squamous cell carcinoma tumor metastasis; microRNA-138 constitutes a promising prognosis biomarker and therapeutic target for oral squamous cell carcinoma with metastasis potential.


Assuntos
Carcinoma de Células Escamosas/genética , Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias Bucais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
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