RESUMO
BACKGROUND & AIMS: Musashi1 (MSI1) belongs to the RNA-binding protein (RBP) family, with functions as translational activator or suppressor of specifically bound mRNA. However, its function in hepatocellular carcinoma (HCC) has been deeply unexplored. Here, we investigated the role of MSI1 for proliferation and tumourigenesis in HCC. METHODS: The expression of MSI1 in HCC tissues was examined by immunohistochemistry and western blotting. The effects of MSI1 overexpression and silencing on cell proliferation, cell viability, tumoursphere and tumour formation of HCC were explored. RESULTS: In this study, we initially reported that MSI1 was upregulated in HCC. Overexpression of MSI1 in HepG2 cell lines resulted in significantly promoted cell growth, tumour formation and cell cycle progression. Consistently, knockdown of MSI1 in Huh7 cell lines remarkably inhibited cell growth and tumour formation, and caused cell cycle arrest at the G1/S transition. Dual-luciferase assays indicated that MSI1 activated Wnt signal pathway, and APC and DKK1 were direct targets of MSI1. CONCLUSION: Taken together, these findings indicate that an oncogenic role of MSI1 in HCC may be through modulation of cell growth and cell cycle by activating Wnt pathway via direct downregulation of APC and DKK1.
Assuntos
Proteína da Polipose Adenomatosa do Colo/metabolismo , Carcinoma Hepatocelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas de Ligação a RNA/metabolismo , Via de Sinalização Wnt , Animais , Carcinogênese , Ciclo Celular , Proliferação de Células , Células HeLa , Células Hep G2 , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de NeoplasiasRESUMO
EphB2, a receptor tyrosine kinase for ephrin ligands, is overexpressed in various cancers and plays an important role in tumor progression. However, the expression and functions of EphB2 in cervical cancer remain unknown. In this study, we performed immunohistochemistry in clinical cervical specimens and found that EphB2 was overexpressed in the cervical cancer specimens, and its expression correlated with cancer progression. The percentage of EphB2-positive cells increased gradually from 28% in the normal cervix to 40% in high-grade squamous intraepithelial lesions, and ultimately to 69.8% in squamous cell carcinomas (P < .05). We overexpressed EphB2 in HeLa cells and silenced EphB2 in cervical cancer (C33A) cells, which expressed low and high levels of EphB2, respectively. Exogenous EphB2 promoted cell migration, invasion, and an epithelial-mesenchymal transition (EMT) signature, which is a complex process that occurs during organogenesis and cancer metastasis, whereas EphB2 silencing had the opposite effect (P < .05). Furthermore, HeLa cells with exogenous EphB2 exhibited a stem cell-like state that promoted tumorsphere formation in vitro and exhibited tumorigenesis potential in vivo (P < .05), whereas EphB2 silencing in C33A cells inhibited these stem cell properties (P < .05). In addition, we investigated the intracellular signaling pathways in cervical cancer and found that R-Ras expression correlated positively with EphB2 in clinical samples, and its activity was regulated by EphB2 in cervical cancer. These findings demonstrate that EphB2 plays an important role in cervical cancer progression by orchestrating an EMT program through R-Ras activation.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Transição Epitelial-Mesenquimal , Receptor EphB2/biossíntese , Neoplasias do Colo do Útero/genética , Adulto , Animais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Colo do Útero/metabolismo , Colo do Útero/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Genes ras , Células HeLa , Humanos , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Transdução de Sinais/fisiologia , Células-Tronco/citologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologiaRESUMO
OBJECTIVE: Aldehyde dehydrogenase (ALDH) has recently been reported as a marker of cancer stem-like cells in ovarian cancer. However, the prognostic role of ALDH in ovarian cancer still remains controversial. In this study, we aimed to evaluate the association between the expression of ALDH and the outcome of ovarian cancer patients by performing a meta-analysis. METHODS: We systematically searched for studies investigating the relationships between ALDH expression and outcome of ovarian cancer patients. Only articles in which ALDH expression was detected by immunohistochemical staining were included. A meta-analysis was performed to generate combined hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 1,258 patients from 7 studies (6 articles) were included in the analysis. Our results showed that high ALDH expression in patients with ovarian cancer was associated with poor prognosis in terms of Os (HR, 1.25; 95% CI, 1.07-1.47; P = 0.005) and DFS (HR, 1.58; 95% CI, 1.00-2.49; P = 0.052), though the difference for DFS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg's and Egger's tests (Begg's test, P = 0.707; Egger's test, P = 0.355). CONCLUSION: The present meta-analysis indicated that elevated ALDH expression was associated with poor prognosis in patients with ovarian cancer.