RESUMO
MicroRNA-30e (miR-30e) is downregulated in various tumor types. However, its mechanism in inhibiting tumor growth of breast cancer remains to be elucidated. In this study, we found that miR-30e was significantly downregulated in tumor tissues of breast cancer (BC) patients and cell lines, and overexpression of miR-30e inhibited cell proliferation, migration and invasion. To understand the potential mechanism of miR-30e in inhibiting tumor growth, we showed that miR-30e blocked the activation of AKT and ERK1/2 pathways, and the expression of HIF-1α and VEGF via directly targeting IRS1. Moreover, miR-30e regulates cell proliferation, migration, invasion and increases chemosensitivity of MDA-MB-231 cells to paclitaxel by inhibiting its target IRS1. MiR-30e also inhibited tumor growth and suppressed expression of IRS1, AKT, ERK1/2 and HIF-1α in mouse xenograft tumors. To test the clinical relevance of these results, we used 40 pairs of BC tissues and adjacent normal tissues, analyzed the levels of miR-30e and IRS1 expression in these tissues, and found that miR-30e levels were significantly inversely correlated with IRS1 levels in these BC tissues, suggesting the important implication of our findings in translational application for BC diagnostics and treatment in the future.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos , Proteínas Substratos do Receptor de Insulina/metabolismo , MicroRNAs/metabolismo , Animais , Sequência de Bases , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND & OBJECTIVE: Mucoepidermoid carcinoma of nasopharynx, a kind of primary adenocarcinoma of nasopharynx, is rare, and has seldom been reported. This article was to summarize the pathogenesis, clinical features, and treatment outcomes of this disease according to our experiences. METHODS: From Jan. 1975 to Dec. 2003, 12 patients with pathologically confirmed primary mucoepidermoid carcinoma of nasopharynx were treated in our hospital. We analyzed retrospectively their clinical data with literature review. RESULTS: The 12 patients with mucoepidermoid carcinoma of nasopharynx accounted for only 0.026% of all nasopharyngeal cancer patients diagnosed simultaneously in our hospital. Age of getting disease was 20 to 60 years old with male to female ratio of 2:1. Positive rates of Epstein-Barr virus serological tests (VCA-IgA, EA-IgA, and DNA enzyme ratio) were very low [50.0% (6/12), 11.1% (1/9), and 20.0% (1/5)]. Of the 11 patients with follow-up data, 4 received chemotherapy, 4 received surgery plus radiotherapy, and 3 received radiochemotherapy. The 5-, and 10-year survival rates of the 12 patients were 27.3%, and 9.0%. CONCLUSIONS: Mucoepidermoid carcinoma of nasopharynx is a special type of nasopharyngeal carcinoma with specific pathogenesis features. Surgery-predominant of complete lumpectomy combined treatment strategy is possibly accommodating.
