Background Isoliquiritigenin (ISL) is a natural compound in licorice and has chemopreventive and anti-tumour activities. ISL induces tumour cell apoptosis and DNA damage in cervical cancer cells, and induces ATM-associated DNA repair signalling. However, ISL down-regulates ATM and phosphorylated ATM (p-ATM) in human oral squamous cell carcinoma (OSCC) cell lines. The aim of this study was to investigate the ATM inhibition mechanism of ISL in OSCC cell lines. Methods mRNA and protein expression were detected by reverse transcription-PCR (RT-PCR) and western blotting, respectively. The promoter activity was detected by firefly and renilla luciferase reporter system. DNA damage was analysed by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay and gamma-H2A.X protein expression. microRNA expression was detected by quantitative RT-PCR. Findings ISL induced OSCC cell cycle G2/M phase arrest, apoptosis, and DNA damage. However, the DNA repair-associated ATM and p-ATM proteins were down-regulated, ATM mRNA levels were unchanged, and the p-ATM downstream signals were inhibited. The down-regulated ATM protein expression might be caused by promoter activity inhibition, microRNA over-expression, and protein degradation. The ATM promoter in OSCC cell line was unchanged after ISL treatment. The microRNAs miR203a and miR421, which target ATM, were both down-regulated. When blocking caspase activity with Z-DVED-FMK, the down-regulation of ATM was reversed. Interpretation ISL-inhibited ATM expression was not regulated by miR203a and miR421 at a transcriptional level. The down-regulation of ATM was caused by ISL activating caspase. These data indicate that ISL induced apoptosis and inhibited DNA repair in OSCC. ISL might be a promising chemopreventive agent against oral cancer. Isoliquiritigenin (ISL) is a natural compound in licorice and has chemopreventive and anti-tumour activities. ISL induces tumour cell apoptosis and DNA damage in cervical cancer cells, and induces ATM-associated DNA repair signalling. However, ISL down-regulates ATM and phosphorylated ATM (p-ATM) in human oral squamous cell carcinoma (OSCC) cell lines. The aim of this study was to investigate the ATM inhibition mechanism of ISL in OSCC cell lines. mRNA and protein expression were detected by reverse transcription-PCR (RT-PCR) and western blotting, respectively. The promoter activity was detected by firefly and renilla luciferase reporter system. DNA damage was analysed by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay and gamma-H2A.X protein expression. microRNA expression was detected by quantitative RT-PCR. ISL induced OSCC cell cycle G2/M phase arrest, apoptosis, and DNA damage. However, the DNA repair-associated ATM and p-ATM proteins were down-regulated, ATM mRNA levels were unchanged, and the p-ATM downstream signals were inhibited. The down-regulated ATM protein expression might be caused by promoter activity inhibition, microRNA over-expression, and protein degradation. The ATM promoter in OSCC cell line was unchanged after ISL treatment. The microRNAs miR203a and miR421, which target ATM, were both down-regulated. When blocking caspase activity with Z-DVED-FMK, the down-regulation of ATM was reversed. ISL-inhibited ATM expression was not regulated by miR203a and miR421 at a transcriptional level. The down-regulation of ATM was caused by ISL activating caspase. These data indicate that ISL induced apoptosis and inhibited DNA repair in OSCC. ISL might be a promising chemopreventive agent against oral cancer.

Introduction: Recently, increasing evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of diverse cellular processes such as cell growth, differentiation, cell cycle progression, and apoptosis. Additionally, several lncRNAs are frequently aberrantly expressed in various human cancers, with both oncogenic and tumor suppressive potential roles. Nevertheless, just a few reports addressed the role of lncRNAs in hepatocellular carcinoma (HCC) progression. In this study, we tried to identify and characterize the role of lncRNA-AOC4P in the regulation of hepatocarcinogenesis. Methods: The expression level of AOC4P was examined in 121 paired HCC and para-tumoral liver tissues using quantitative real-time RT-PCR. The correlation between AOC4P levels, clinical parameters, and survival outcomes were analyzed to elucidate the clinical significance of AOC4P in HCC. In vitro and in vivo functional assays were also performed to dissect the underlying mechanisms. Results: The expression of AOC4P was significantly downregulated in HCC tissues and low expression of AOC4P correlated with poor prognostic outcomes. Furthermore, in vitro functional assays indicated that AOC4P significantly reduced cell proliferation, migration and invasion ability through inhibiting epithelial-mesenchymal transition. The in vivo animal model also demonstrated the tumor suppressor role of AOC4P via reducing tumor growth and metastasis. Conclusion: AOC4P may act as a tumor suppressor in HCC by reduced cell proliferation, migration and invasion ability through suppressing epithelial-mesenchymal transition. The findings could help us to further understand the mechanism of HCC progression and to develop new therapeutic strategies for HCC.

DNA microaarays are popular tools for large-scale analysis of gene expression in the brain. Combine laser capture microdisection and quantitative real-time reverse transcription polymerase chain reaction technologies, such large-scale expression analysis can be successfully addressed in well-defined tissue specimens. We analyzed the gene expression patterns in three glioblastoma tissue and two control brain samples obtained from the operation by dye-swapping method using cDNA microarray. The differential expression of approximately 4,192 cDNAs was examined. Data after normalization, there are 7 up regulation genes, and 34 down regulation genes, which are 3 times of microarray expression values more or less then the control.

Objective Conventional chromosomal studies or fluorescent in situ hybridization takes days to diagnose fetal aneuploidies during amniocentesis. Here, we evaluated the value of mass spectrometry-based clinical proteomics analysis on amniotic fluid supernatant (AFS) as a rapid detection of fetal aneuploidies.Methods Proteomics profiles generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after fractionating samples with functionalized magnetic beads were used for differentiating 60 normal karyotypic from 20 aneuploid AFS. After the discriminating models were generated using genetic algorithm, we evaluated the clinical efficacy of the models in detecting aneuploidies in two batches (each n = 30) of AFS prior to the release of chromosomal diagnoses.Results Within hours, the two-step proteomics analysis of AFS with the C18 model, followed by the weak cation exchange model, was able to detect aneuploid AFS at 3.3% disease prevalence rate with 100% sensitivity, 72 to 96% specificity, I I to 50% positive predictive value, and 100% negative predictive value.Conclusion Clinical proteomics analysis of AFS using magnetic beads-based sample preparation and MALDI-TOF-MS can be used as a rapid detection for fetal aneuploidies. With perfect sensitivity and negative predictive value of the two-step proteomics method, it may be used for rapid detection of aneuploid AFS immediately after amniocentesis. Further large-scale examinations are apparently needed to verify the clinical value of this rapid detection. Copyright (c) 2005 John Wiley & Sons, Ltd.