RESUMO
The molecular mechanisms governing the metastasis of colorectal cancer (CRC) are incompletely understood. In the present study, we found NOVA1 to be expressed at higher levels in CRC cell lines and tissue samples, and this upregulation was positively correlated with TNM stage (pâ¯=â¯0.034), poor differentiation (pâ¯=â¯0.001), and lymph node metastasis (pâ¯=â¯0.008). Both overall survival (OS) and relapse-free survival (RFS) were both significantly decreased in patients with high NOVA1 expression relative to those with low expression. Through a multivariate analysis, we determined that NOVA1 independently predicted poor outcomes in those with CRC. In further functional studies, we found that NOVA1 expression controlled the proliferation and invasive characteristics of CRC cells via a mechanism wherein NOVA1 bound and stabilized the IL6 mRNA, enhancing IL-6/JAK2/STAT3 signaling to in turn upregulate matrix metalloproteinases (MMPs) 2, 7, and 9. NOVA1 therefore plays key functional roles in regulating CRC progression, and our results further indicate that it serve as a valuable prognostic biomarker and potentially a target for therapeutic treatment in individuals with CRC.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-6/genética , Janus Quinase 2/metabolismo , Neoplasias Pulmonares/secundário , Proteínas de Ligação a RNA/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinase 2/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Antígeno Neuro-Oncológico Ventral , Prognóstico , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Fator de Transcrição STAT3/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: MicroRNAs (miRNAs) play an important regulatory role in carcinogenesis and cancer progression. Aberrant expression of miR-497-5p has been reported in various human malignancies. However, the role of miR-497-5p in hepatocellular carcinoma (HCC) remains unclear. RESULTS: In this study, we found that miR-497-5p was downregulated in HCC tissues. The low level of miR-497-5p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. The overexpression of miR-497-5p significantly inhibited HCC cell proliferation, colony formation, and metastasis in vitro and vivo. Bioinformatics analysis further identified insulin-like growth factor 1 (IGF1) as a novel target of miR-497-5p in HCC cells. CONCLUSION: Our study suggested that miR-497-5p regulates HCC cell survival, partially through downregulation of IGF1. Therefore, the miR-497-5p/IGF1 axis might serve as a novel therapeutic target in patients with HCC.
