BackgroundCentromere protein A (CENP-A) plays important roles in cell-cycle regulation and genetic stability. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).Methodology/Principal FindingsCENP-A expression at the mRNA and protein levels was examined in 20 pairs of fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for CENP-A was performed on 80 paraffin-embedded HCC specimens, and the clinical significance of its expression was analyzed. A human HCC cell line HepG2 with high abundance of CENP-A was used to study the effects of manipulating CENP-A on HCC growth. Quantitative real-time polymerase chain reaction arrays and Western blot analysis were employed to identify the cell-cycle control- and apoptosis-related genes regulated by CENP-A. The results showed that CENP-A was aberrantly overexpressed in HCCs relative to adjacent nontumor tissues. This overexpression was significantly associated with positive serum HBsAg status, increased histological grade, high Ki-67 index and P53 immunopositivity. Knockdown of CENP-A in HepG2 cells reduced cell proliferation, blocked cell cycle at the G1 phase, and increased apoptosis. The antiproliferative effects of CENP-A silencing were also observed in vivo. Conversely, CENP-A overexpression promoted HCC cell growth and reduced apoptosis. Furthermore, many genes implicated in cell-cycle regulation and apoptosis, including CHK2, P21waf1, P27 Kip1, SKP2, cyclin G1, MDM2, Bcl-2, and Bax, were deregulated by manipulating CENP-A.Conclusions/SignificanceOverexpression of CENP-A is frequently observed in HCC. Targeting CENP-A can inhibit HCC growth, likely through the regulation of a large number genes involved in cell-cycle progression and apoptosis, and thereby represents a potential therapeutic strategy for this malignancy.
Background
Emerging evidence has shown that dysregulated expression of long noncoding RNAs (lncRNAs) is implicated in liver hepatocellular carcinoma (HCC). However, the role and molecular mechanism of differentially expressed lncRNAs in HCC has not been fully explained.
Methods
The expression profiles of lncRNAs in HCC samples were derived from microarrays analysis or downloaded from The Cancer Genome Atlas (TCGA), and their correlation with prognosis and clinical characteristics were further analyzed. Silencing of lncRNA ZFPM2-AS1 was conducted to assess the effect of ZFPM2-AS1 in vitro. The miRcode and Target Scan databases were used to determine the lncRNA-miRNA-mRNA interactions. The biological functions were demonstrated by luciferase reporter assay, western blotting, PCR and rescue experiments.
Results
The expression level of lncRNA ZFPM2-AS1 was significantly higher in HCC tissues than in adjacent normal tissues, and higher ZFPM2-AS1 was remarkably related to poor survival. Functionally, silencing of lncRNA ZFPM2-AS1 inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. Bioinformatics analysis based on the miRcode and TargetScan databases showed that lncRNA ZFPM2-AS1 regulated GDF10 expression by competitively binding to miR-139. miR-139 and downregulated GDF10 reversed cell phenotypes caused by lncRNA ZFPM2-AS1 by rescue analysis.
Conclusions
ZFPM2-AS1, an upregulated lncRNA in HCC, was associated with malignant tumor phenotypes and worse patient survival. ZFPM2-AS1 regulated the progression of HCC by acting as a competing endogenous RNA (ceRNA) to competitively bind to miR-139 and regulate GDF10 expression. Our study provides new insight into the posttranscriptional regulation mechanism of lncRNA ZFPM2-AS1 and suggests that ZFPM2-AS1/miR-139/GDF10 may act as a potential therapeutic target and prognostic biomarker for HCC.
The basic helix-loop-helix (bHLH) proteins are a superfamily of transcription factors that play important roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in a dozen of organisms including fruit fly, mouse and human. We identified 52 bHLH members in silico in the silkworm genome. Phylogenetic analyses revealed that they belong to 39 bHLH families with 21, 10, 12, 1, 7 and 1 members in groups A, B, C, D, E and F, respectively. Genes that encode ASCb, NeuroD, Oligo, MyoRb, Figalpha and Mad were not found in the silkworm genome. The present study provides important background information for future studies using the silkworm as a model system for insect development. Besides, the in-group phylogenetic analysis was demonstrated to be effective in classifying identified bHLH sequences into corresponding families, which can be helpful in the classification of bHLH members of other organisms.
A novel
magnetic intercalation Fe3O4-QDs@g-C3N4/ATP photocatalyst was first prepared by a combined
eutectic method with deposition technology; it shows superior degradation
efficiency for removing 2-mercaptobenzothiazole (MBT)
under visible light. The improved photocatalytic performance is mainly
attributed to the intercalation effect of attapulgite (ATP) in g-C3N4 together with the quantum effect of Fe3O4 quantum dots (QDs) and the better conductivity between
ATP and g-C3N4 resulting in the enhanced separation
efficiency of photogenerated electron–hole pairs in the light
absorption range. Moreover, insight into this mechanism indicates
that the holes and superoxide radicals are the major active species
in the MBT removal procedure. This work provides an efficient and
promising approach to construct new high-performance g-C3N4-based photocatalytic materials for wastewater treatment.
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