RESUMO
BACKGROUND: Increasing evidence has suggested that miR-330-5p can function as a tumor suppressor in different types of cancers. However, the effects and underlying mechanisms of miR-330-5p in the development of cutaneous malignant melanoma (CMM) remain largely unknown. The aim of the present study was to investigate the role of miR-330-5p in CMM and to determine the molecular mechanisms underlying its action. MATERIALS AND METHODS: The expression level of miR-330-5p was detected in 26 cases of primary CMM tissues and cell lines by real-time quantitative polymerase chain reaction. We also assessed whether overexpression of miR-330-5p influences in vitro cell proliferation, invasion, and migration. Western blotting analysis was used to detect the influence of miR-330-5p on the targets, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-330-5p in CMM tissues. RESULTS: Our study showed that miR-330-5p was downregulated in CMM tissues (P = 0.010) and cell lines (P < 0.05), and patients with high mitotic activity showed lower miR-330-5p expression levels (P = 0.002). Enforced expression of miR-330-5p inhibits malignant CMM cells proliferation and migration and led to downregulation of the TYR and PDIA3 protein. Moreover, the expression level of miR-330-5p in CMM tissues showed inverse relationship with the expression level of TYR and PDIA3 protein. CONCLUSIONS: In conclusion, our findings suggested that miR-330-5p represents a potential tumor-suppressive miRNA and plays an important role in CMM progression by suppressing TYR and PDIA3 expression.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Melanoma/genética , MicroRNAs/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Neoplasias Cutâneas/genética , Biomarcadores Tumorais/genética , Western Blotting , Linhagem Celular , Movimento Celular , Proliferação de Células/genética , Regulação para Baixo , Humanos , Melanoma/metabolismo , Melanoma/patologia , Invasividade Neoplásica , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Regulação para Cima , Melanoma Maligno CutâneoRESUMO
AIMS: MicroRNA-186 (miR-186) has been shown to be involved in various types of cancer. The purpose of this study was to investigate the expression level and functional role of miR-186 in human cutaneous malignant melanoma cells. SUBJECTS AND METHODS: Expression of miR-186 was analyzed in human cutaneous malignant melanoma (CMM) cell lines SK-MEL-1, G-361, A375 and A875, and human normal epidermal melanocytes cell line HEMn-LP by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additionally, the functional role of miR-186 on melanoma cells was investigated by transfection of miR-186 mimic followed by analyses of cell proliferation, apoptosis, and metastasis. RESULTS: We found that the expression levels of miR-186 were decreased in CMM cell lines compared with normal epidermal melanocytes cell line. Moreover, overexpression of miR-186 inhibited cells proliferation through abrogating the G1-S transition, and reduced cells migration and invasion. CONCLUSIONS: Our findings suggested that miR-186 exhibit an inhibitory effect on CMM cell proliferation, migration, and invasion; thus, may serve as a potential therapeutic target for human CMM intervention.
Assuntos
Melanoma/genética , MicroRNAs/genética , Interferência de RNA , Neoplasias Cutâneas/genética , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia , Transfecção , Melanoma Maligno CutâneoRESUMO
Dysregulation of microRNA plays critical roles in various malignancies. However, whether the aberrant expression of miR-215 in breast cancer is associated with malignancy, metastasis, or prognosis remains unknown. In this study, we demonstrated that the relative level of miR-215 expression was lower in cancer tissues compared with adjacent non-malignant tissues (p < 0.001). Low-miR-215 expression was observed to be closely correlated with higher tumor grade (p = 0.008), human epidermal growth factor receptor 2 (HER2) positivity (p = 0.006), HER2 positive breast cancer subtype (p = 0.016), and lymph node metastasis (p = 0.039). Moreover, patients with low-miR-215 expression showed shorter 5-year disease-specific survival (DSS) than the high-miR-215 expression group (p = 0.007). Multivariate analysis results revealed that miR-215 downexpression was an unfavorable prognostic factor for DSS in addition to tumor size, ER, and lymph node metastasis. Our results support the potential of miR-215 as a prognostic predictor for breast cancer with its high expression in cancer tissues and its relationship with other clinicopathologic factors and survival.