ABSTRACT
Hepatocellular carcinoma (HCC) contributes to cancer-related deaths greatly every year in the world. However, there is still no radical method for HCC treatment. Here we screened out a lncRNA FABP5P3 that was up-regulated in HCC tissues. Patients with higher FABP5P3 expression displayed poorer survival rate. FABP5P3 depletion in HCC cell lines and sample cells remarkably inhibited the abilities of proliferation, migration and invasion. In mechanism, we showed that FABP5P3 bond to miR-589-5p which served as a tumor suppressor. MiR-589-5p targeted directly the mRNA of ZMYND19 whose function has not been defined in HCC. FABP5P3 promoted HCC development and progression by sponging miR-589-5p and up-regulating ZMYND19 expression. In sum, we showed that FABP5P3/miR-589-5p/ZMYND19 axis regulates cell proliferation and migration in HCC, which may serve as a new target for HCC treatment.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carrier Proteins/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , MicroRNAs/genetics , Neoplasm Invasiveness/genetics , RNA, Long Noncoding/genetics , Animals , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Disease Progression , Humans , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness/pathology , Signal TransductionABSTRACT
Recently, increasing evidences demonstrate that circular RNAs (circRNAs) exert very important functions in the progression of human cancers. However, the functions and molecular mechanism of circ_0067934 in hepatocellular carcinoma (HCC) are largely unknown. In the present study, we found that the expression of circ_0067934 was significantly upregulated in HCC tissues and cell lines compared to adjacent normal tissues. Furthermore, we showed that circ_0067934 knockdown remarkably suppressed the proliferation, migration and invasion of Hep3B and HuH7 cells while inducing their apoptosis. In terms of mechanism, we found that circ_0067934 directly suppressed miR-1324, which targeted the 3'-UTR of FZD5 mRNA and subsequently downregulated the Wnt/ß-catenin signaling pathway in HCC. Through rescue experiments, we demonstrated that circ_0067934 enhanced the proliferation, migration and invasion of HCC cells by the inhibition of miR-1324 and concomitant activation of FZD5/Wnt/ß-catenin signaling pathway. In summary, the circ_0067934/miR-1324/FZD5/ß-catenin signaling axis might serve as a promising therapeutic target for HCC intervention.
Subject(s)
Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Animals , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement , Disease Progression , Frizzled Receptors/genetics , Humans , Liver/metabolism , Liver/pathology , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Wnt Signaling PathwayABSTRACT
AIM: To assess the prognostic value of c-Met status in colorectal cancer. METHODS: We conducted a search in PubMed, Web of Science, and the Cochrane Library covering all published papers up to July 2014. Only studies assessing survival in colorectal cancer by c-Met status were included. This meta-analysis was performed by using STATA11.0. RESULTS: Ultimately, 11 studies were included in this analysis. Meta-analysis of the hazard ratios (HR) indicated that patients with high c-Met expression have a significantly poorer overall survival (OR) (HR = 1.33, 95%CI: 1.06-1.59) and progression-free survival (PFS) (HR = 1.47, 95%CI: 1.03-1.91). Subgroup analysis showed a significant association between high c-Met expression and poorer overall survival in the hazard ratio reported (HR = 1.41, 95%CI: 1.08-1.74). CONCLUSION: The present meta-analysis indicated that high c-Met expression was associated with poor prognosis in patients with colorectal cancer.
Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/enzymology , Proto-Oncogene Proteins c-met/metabolism , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Disease-Free Survival , Humans , Odds Ratio , Risk Factors , Signal Transduction , Time Factors , Up-RegulationABSTRACT
Theaflavins, the oxidation products of tea polyphenols are important biologically active components of black tea. 6-hydroxydopamine is a pro-parkinsonian neurotoxin. Theaflavins could inhibit the auto-oxidation of 6-hydroxydopamine in a dose-dependent manner from 0.5 µg/ml to 25 µg/ml. Here we investigated the protective effect of theaflavins on 6-hydroxydopamine induced SH-SY5Y cells against apoptosis (within this concentration range). It was found that pretreating SH-SY5Y cells with 0.5 µg/ml of theaflavins prevented 6-hydroxydopamine-induced loss of cell viability, condensed nuclear morphology, attenuated 6-hydroxydopamine-induced apoptosis, decrease of mitochondrial membrane potential and the increase of intracellular nitric oxide levels. Our results indicated that theaflavins had protective effect against 6-hydroxydopamine induced apoptosis at low concentrations, possibly through inhibition of reactive oxygen species and nitric oxide production.
