Up-regulation of CNDP2 facilitates the proliferation of colon cancer

BACKGROUND: Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis. METHODS: We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena. RESULTS: The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E. CONCLUSIONS: Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo

On the relation between the mass of Compact Massive Objects and their host galaxies

Supermassive black holes and/or very dense stellar clusters are found in the central regions of galaxies. Nuclear star clusters are present mainly in faint galaxies while upermassive black holes are common in galaxies with masses $\geq 10^{10}$ M$_\odot$. In the intermediate galactic mass range both types of central massive objects (CMOs) are found. Here we present our collection of a huge set of nuclear star cluster and massive black hole data that enlarges significantly already existing data bases useful to investigate for correlations of their absolute magnitudes, velocity dispersions and masses with structural parameters of their host galaxies. In particular, we directed our attention to some differences between the correlations of nuclear star clusters and massive black holes as subsets of CMOs with hosting galaxies. In this context, the mass-velocity dispersion relation plays a relevant role because it seems the one that shows a clearer difference between the supermassive black holes and nuclear star clusters. The $M_{MBH}-{\sigma}$ has a slope of $5.19\pm 0.28$ while $M_{NSC}-{\sigma}$ has the much smaller slope of $1.84\pm 0.64$. The slopes of the CMO mass- host galaxy B magnitude of the two types of CMOs are indistinguishable within the errors while that of the NSC mass-host galaxy mass relation is significantly smaller than for supermassive black holes. Another important result is the clear depauperation of the NSC population in bright galaxy hosts, which reflects also in a clear flattening of the NSC mass vs host galaxy mass at high host masses.Comment: 12 pages, 22 figures, 2 tables, accepted for publication in MNRA

Down-Regulation of MiR-127 Facilitates Hepatocyte Proliferation during Rat Liver Regeneration

Liver regeneration (LR) after partial hepatectomy (PH) involves the proliferation and apoptosis of hepatocytes, and microRNAs have been shown to post-transcriptionally regulate genes involved in the regulation of these processes. To explore the role of miR-127 during LR, the expression patterns of miR-127 and its related proteins were investigated. MiR-127 was introduced into a rat liver cell line to examine its effects on the potential target genes Bcl6 and Setd8, and functional studies were undertaken. We discovered that miR-127 was down-regulated and inversely correlated with the expression of Bcl6 and Setd8 at 24 hours after PH, a time at which hypermethylation of the promoter region of the miR-127 gene was detected. Furthermore, in BRL-3A rat liver cells, we observed that overexpression of miR-127 significantly suppressed cell growth and directly inhibited the expression of Bcl6 and Setd8. The results suggest that down-regulation of miR-127 may be due to the rapid methylation of its promoter during the first 24 h after PH, and this event facilitates hepatocyte proliferation by releasing Bcl6 and Setd8. These findings support a miRNA-mediated negative regulation pattern in LR and implicate an anti-proliferative role for miR-127 in liver cells

The noncoding RNA HOXD-AS1 is a critical regulator of the metastasis and apoptosis phenotype in human hepatocellular carcinoma

Abstract Background Despite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized. Methods A lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue. Results We observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues. In vitro and in vivo gain- or loss-of-function studies re-affirmed that HOXD-AS1 is able to facilitate cancer metastasis and inhibit apoptosis. Moreover, we identified that HOXD-AS1 upregulated the Rho GTPase activating protein 11A (ARHGAP11A) by competitively binding to microRNA-19a (miR19a), resulting in induced metastasis. Interestingly, the regulator of G-protein signaling 3 (RGS3), a potential inhibitor of the MEK-ERK1/2 signaling axis, was also found to be downregulated by ectopic HOXD-AS1 overexpression, leading to a remarkably reduced apoptotic effect. Conclusions The present investigation strongly indicates that HOXD-AS1 is an oncogenic lncRNA that promotes HCC metastasis and that its pro-metastatic phenotype can partially be attributed to the HOXD-AS1/miR19a/ARHGAP11A signaling axis

MicroRNA-127 Post-Transcriptionally Downregulates Sept7 and Suppresses Cell Growth in Hepatocellular Carcinoma Cells

Background/Aims: Hepatocellular carcinoma is one of the most common cancers worldwide. It has been suggested that microRNAs, a class of small regulatory RNAs, are associated with tumorigenesis by targeting the mRNAs of hundreds of genes that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism, and proliferation. Methods/Results: we analyzed the expression levels of mir-127 in 33 HCC and non-cancerous tissues using qRT-PCR. MiR-127 is downregulated in 69.7% of HCC tissues compared with adjacent normal tissues, but its expression level is not correlated with the TNM stage, AFP level, or age. In vitro, miR-127 can arrest Huh7 at the G2/M phase and inhibit Huh7 cell proliferation. In an in vivo xenograft model, the overexpression of miR-127 can inhibit Huh7 cell tumorigenicity. The luciferase reporter and western blot results confirm that miR-127 downregulates Sept7 expression by targeting its 3'UTR. Furthermore, the knockdown of Sept7 has the same effect on cell proliferation as the overexpression of miR-127 in Huh7 cells. Conclusion: miR-127 plays a tumor-suppressor role and can serve as a potential diagnostic biomarker for HCC

Gelatin versus its two major degradation products, prolyl‐hydroxyproline and glycine, as supportive therapy in experimental colitis in mice

Gelatin is an anti‐inflammatory dietary component, and its predominant metabolites entering circulation are prolyl‐hydroxyproline (Pro‐Hyp) and glycine. We evaluated the protective effects of orally administered gelatin, glycine, and Pro‐Hyp 10:3:0.8 (w/w/w) against dextran sodium sulfate (DSS)‐induced colitis in mice. According to clinical, histological, and biochemical parameters, they exhibited significant activities in the order of gelatin < glycine < Pro‐Hyp. Gelatin prevented the DSS‐induced increase in interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) in the colon, rather than in peripheral blood. Glycine and Pro‐Hyp attenuated the DSS‐induced rise in colonic IL‐6 and TNF‐α, as well as peripheral IL‐1β, IL‐6, and TNF‐α. Hematologic results show the attenuation of DSS‐induced leukocytosis and lymphocytosis by glycine and Pro‐Hyp, rather than gelatin. These findings suggest that glycine and Pro‐Hyp constitute the material basis for gelatin's anticolitis efficacy, and they have better anticolitis activities and distinct mechanisms of action when ingested as free compounds than as part of gelatin

miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma

AbstractMicroRNAs are known to be involved in the pathogenesis of hepatocellular carcinoma (HCC). This study aims to explore the potential biological function of miR-376a, which was found to be inhibited after partial hepatectomy, in HCC. We discovered that miR-376a was frequently down-regulated in HCC cell lines and HCC tissues, while higher relative level of miR-376a was significantly associated with high serum AFP level. Over-expression of miR-376a not only inhibited proliferation but induced apoptosis in Huh7 cells. Additionally, p85α (PIK3R1) was identified as a direct and functional target of miR-376a in Huh7 cells. Moreover, we confirmed that p85α and miR-376a were inversely correlated in HCC. These findings suggest that down-regulation of miR-376a may contribute to the development of HCC by targeting p85α

Mir-34a is upregulated during liver regeneration in rats and is associated with the suppression of hepatocyte proliferation

Background: MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination. Methodology/Principal Finding: MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin bB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver. Conclusion/Significance: MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34amediate

Orally administered gold nanoparticles protect against colitis by attenuating Toll-like receptor 4- and reactive oxygen/nitrogen species-mediated inflammatory responses but could induce gut dysbiosis in mice

Abstract Background Gold nanoparticles (AuNPs) are attracting interest as potential therapeutic agents to treat inflammatory diseases, but their anti-inflammatory mechanism of action is not clear yet. In addition, the effect of orally administered AuNPs on gut microbiota has been overlooked so far. Here, we evaluated the therapeutic and gut microbiota-modulating effects, as well as the anti-inflammatory paradigm, of AuNPs with three different coatings and five difference sizes in experimental mouse colitis and RAW264.7 macrophages. Results Citrate- and polyvinylpyrrolidone (PVP)-stabilized 5-nm AuNPs (Au-5 nm/Citrate and Au-5 nm/PVP) and tannic acid (TA)-stabilized 5-, 10-, 15-, 30- and 60-nm AuNPs were intragastrically administered to C57BL/6 mice daily for 8 days during and after 5-day dextran sodium sulfate exposure. Clinical signs and colon histopathology revealed more marked anti-colitis effects by oral administration of Au-5 nm/Citrate and Au-5 nm/PVP, when compared to TA-stabilized AuNPs. Based on colonic myeloperoxidase activity, colonic and peripheral levels of interleukin-6 and tumor necrosis factor-α, and peripheral counts of leukocyte and lymphocyte, Au-5 nm/Citrate and Au-5 nm/PVP attenuated colonic and systemic inflammation more effectively than TA-stabilized AuNPs. High-throughput sequencing of fecal 16S rRNA indicated that AuNPs could induce gut dysbiosis in mice by decreasing the α-diversity, the Firmicutes/Bacteroidetes ratio, certain short-chain fatty acid-producing bacteria and Lactobacillus. Based on in vitro studies using RAW264.7 cells and electron spin resonance oximetry, AuNPs inhibited lipopolysaccharide (LPS)-triggered inducible nitric oxide (NO) synthase expression and NO production via reduction of Toll-like receptor 4 (TLR4), and attenuated LPS-induced nuclear factor kappa beta activation and proinflammatory cytokine production via both TLR4 reduction and catalytic detoxification of peroxynitrite and hydrogen peroxide. Conclusions AuNPs have promising potential as anti-inflammatory agents; however, their therapeutic applications via the oral route may have a negative impact on the gut microbiota