RESUMO
PURPOSE: Long non-coding RNA (LncRNA) urothelial carcinoma-associated 1 (UCA1) is reported to be dysregulated in hepatocellular carcinoma (HCC) progression. However, the functions of UCA1 in HCC still need further study. The aim is to detect the role of UCA1 involving in HCC cells proliferation and invasion, and epithelial-mesenchymal transition (EMT). METHODS: The quantitative real-time PCR was used to detect the UCA1 and miR-203 expression levels in 60 cases' HCC tissues and adjacent normal tissues. Western blotting analysis was performed to detect the EMT markers E-cadherin, Vimentin and transcription factor Snail1, Snail2 expression. Luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays were used to evaluate whether miR-203 was a target of UCA1. RESULTS: Our results showed that UCA1 was markedly upregulated in HCC tissues and higher UCA1 expression in HCC was positively associated with tumor size, vascular invasion and American Joint Committee on Cancer (AJCC) stage (P < 0.05). Furthermore, gain-of-function and loss-of-function analysis showed that UCA1 knockdown inhibited HCC cells proliferation and invasion in vitro and xenograft tumour growth in vivo. Moreover, UCA1 overexpression promoted cell epithelial-mesenchymal transition (EMT) in HCC via effectively sponging to miR-203 and thereby activating the expression of transcription factor Snail2. CONCLUSIONS: Our results identified that UCA1/miR-203/Snail2 pathway might involve in HCC progression. Inhibition of UCA1 acted as a promising therapeutic target for HCC patients.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/fisiologia , Fatores de Transcrição da Família Snail/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma Hepatocelular/patologia , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Células Tumorais CultivadasRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) play widespread roles in gene regulation and cellular processes. However, the functional roles of lncRNAs in hepatocellular carcinoma (HCC) are not yet well elucidated. The aim of the present study was to measure the levels of lncRNA PCAT-1 expression in HCC and evaluate its clinical significance in the development and progression of HCC. METHODS: We examined the expression of PCAT-1 in 117 HCC tissues and adjacent non-tumor tissues using quantitative real-time-PCR and analyzed its correlation with the clinical parameters. RESULTS: Our data showed that PCAT-1 expression in HCC tissues was significantly increased compared with adjacent non-tumor tissues (P<0.05). Up-regulated expression of PCAT-1 was significantly associated with TNM stage and metastasis (P<0.05), but not other clinical parameters. Moreover, Kaplan-Meier survival analysis showed that a high expression level of PCAT-1 resulted in a significantly poor overall survival of HCC patients. The multivariate Cox regression analysis demonstrated that PCAT-1 expression level was an independent prognostic factor for the overall survival rate of HCC patients. CONCLUSIONS: Our data suggested that the increased expression of PCAT-1 was associated with advanced clinical parameters and poor overall survival of HCC patients, indicating that PCAT-1 up-regulation may serve as a novel biomarker of poor prognosis in HCC patients.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/terapia , Distribuição de Qui-Quadrado , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND AND AIMS: Matrix metalloproteinase 14 (MMP14) has been identified to play a significant role in several types of cancers, but little is known about the significance of MMP14 in nasopharyngeal carcinoma (NPC) patients. The aim of this study was to explore the association of MMP14 expression with clinicopathologic features and prognosis in NPC. METHODS: MMP14 mRNA and protein expressions were examined in NPC and nasopharyngeal tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of MMP14 expression levels with clinical features and prognosis of NPC patients was analyzed. RESULTS: MMP14 mRNA expression was markedly higher in NPC tissues than in nasopharyngeal epithelium tissues (p = 0.002). Using immunohistochemistry, staining for MMP14 protein was found in the normal nasopharyngeal epithelial cells and malignant epithelial cells, but increased expression of MMP14 was observed in NPC samples compared with normal nasopharyngeal epithelium samples (p = 0.027). In addition, high levels of MMP14 protein were positively correlated with the status of clinical stage (p = 0.009), N classification (p = 0.006), and distant metastasis (p = 0.005) of NPC patients. Patients with higher MMP14 expression had a significantly shorter overall survival time than did patients with low MMP14 expression. Multivariate analysis indicated that the level of MMP14 expression was an independent prognostic indicator (p < 0.001) for the survival of patients with NPC. CONCLUSIONS: MMP14 overexpression is a potentially unfavorable prognostic factor for NPC patients.