RESUMO
Melanoma is responsible for the majority of deaths caused by skin cancer. Antitumor activity of microRNA-329 (miR-329) has been seen in several human cancers. In this study, we identify whether miR-329 serves as a candidate regulator in melanoma. Melanoma-related differentially expressed genes were screened with its potential molecular mechanism predicted. Melanoma tissues and pigmented nevus tissues were collected, where the levels of miR-329 and high-mobility group box 2 (HMGB2) were determined. To characterize the regulatory role of miR-329 on HMGB2 and the ß-catenin pathway in melanoma cell activities, miR-329 mimics, miR-329 inhibitors, and siRNA-HMGB2 were transfected into melanoma cells. Cell viability, migration, invasion, cell cycle, and apoptosis were assessed. miR-329 was predicted to influence melanoma by targeting HMGB2 via the ß-catenin pathway. High level of HMGB2 and low miR-329 expression were observed in melanoma tissues. HMGB2 was targeted and negatively regulated by miR-329. In melanoma cells transfected with miR-329 mimics or siRNA-HMGB2, cell proliferation, migration, and invasion were impeded, yet cell cycle arrest and apoptosis were promoted, corresponding to decreased levels of ß-catenin, cyclin D1, and vimentin and increased levels of GSK3ß and E-cadherin. Collectively, our results show that miR-329 can suppress the melanoma progression by downregulating HMGB2 via the ß-catenin pathway.
Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Proteína HMGB2/metabolismo , Melanoma/metabolismo , MicroRNAs/metabolismo , Neoplasias Cutâneas/metabolismo , beta Catenina/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Apoptose , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Glicogênio Sintase Quinase 3 beta/genética , Proteína HMGB2/genética , Humanos , Masculino , Melanoma/genética , Melanoma/patologia , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Transdução de Sinais , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Vimentina/genética , Vimentina/metabolismo , beta Catenina/genéticaRESUMO
OBJECTIVE: To compare the survival outcomes of early-stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT). STUDY DESIGN: Retrospective observational study. SETTING: Publicly available database. METHODS: A total of 1877 patients with T1-2N0-1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42-3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50-5.02; p = .001). In the HPV-positive cohort, definitive RT and upfront surgery could achieve similar cancer-specific and noncancer survival outcomes. CONCLUSION: Upfront surgery is associated with lower cancer-specific and noncancer mortality in HPV-negative early-stage OPC patients. However, in the setting of HPV-positive early-stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer-specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Prognóstico , Medição de Risco , Neoplasias de Cabeça e Pescoço/complicaçõesRESUMO
Some microRNAs (miRNAs) have been shown to act as oncogenes or tumor suppressor genes in human melanomas. miR-328 is upregulated in blood cells of melanoma patients compared to in healthy controls. This suggests a role for miR-328 in melanoma that warrants investigation. In this study, we demonstrated miR-328 levels to be dramatically decreased in human melanoma cell lines. Moreover, forced expression of miR-328 inhibited proliferation and induced G1-phase arrest of the SK-MEL-1 melanoma cell line. We identified TGFß2 as a direct target gene for miR-328 using a fluorescent reporter assay and western blotting. Levels of TGFß2 were dramatically increased in human melanoma cell lines and were inversely correlated with the miR-328 expression level. Our findings provide new insights into the mechanisms of human melanoma development, indicating that miR-328 has therapeutic potential for this disease.