RESUMO
The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.
Assuntos
Neoplasias Ósseas/secundário , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Reprodutibilidade dos Testes , Regulação para CimaRESUMO
BACKGROUND & OBJECTIVE: Appendix carcinoid tumor is a rare disease, and lack of classic clinical features. This study was to explore clinical characteristics and treatment principles of appendix carcinoid tumor. METHODS: Clinical data, surgical procedures, and prognosis of 13 patients with appendix carcinoid tumor received appendectomy from 1985 to 2000 in our hospital were analyzed retrospectively. RESULTS: The diagnosis was established through operation and pathology. Patients with appendix carcinoid tumor comprised 0.29% of 4483 patients underwent appendectomy during the same period. The tumors were located at the tip and the middle of appendix in 12 patients(92.3%). The diameter of tumor in 12 patients(92.3%) was less than 2 cm. Single appendectomy was performed on 11 patients, right-side colonectomy was performed on 2 patients. Nine patients were alive and remained free of tumor recurrence and metastasis, 3 were lost of follow up, and 1 died of heart disease. The 5-year survival rate is 100%. CONCLUSIONS: Appendix carcinoid tumor has no specific clinical symptom, and located at the tip and the middle of appendix; tumor with diameter of < 1 cm may be resected by single appendectomy.
