Programmed cell death 4 (PDCD4) suppresses metastastic potential of human hepatocellular carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is a lethal malignancy with high rate of metastasis and poor prognosis. There are no effective managements to block metastasis of HCC. Programmed cell death 4 (PDCD4) is found to be a tumor transformation suppressor. Among investigations on effects of PDCD4, little is about the metastatic potentials of HCC cells. This study was to investigate the role of PDCD4 on metastatic potential of human HCC cells.</p> <p>Methods</p> <p>We examined the expression of PDCD4 in three HCC cell lines with different metastatic potentials, MHCC-97H (high metastatic potential), MHCC-97L (low metastatic potential) and Hep3B (no metastatic potential). A plasmid encoding PDCD4 gene was constructed and then transfected into HCC cells with the lowest PDCD4 expression level. Effects of PDCD4 on cell proliferation, cell apoptosis, gene expression of metastasis tumor antigen 1 (MTA1) and in vitro migration and invasion capacity were assessed after transfection.</p> <p>Results</p> <p>Our results showed that the expression level of PDCD4 was inversely correlated to the metastatic potential of HCC cells. After transfection with the PDCD4 gene, HCC cell proliferation rate was significantly decreased, cell apoptosis rate was significantly increased, the expression of MTA1 gene, HCC cell migration and Matrigel invasion were also remarkably inhibited.</p> <p>Conclusion</p> <p>PDCD4 expression is inversely correlated to the metastatic potential of HCC cells. PDCD4 can effectively suppress the metastatic potential of HCC cells.</p

Expression of the microRNA-143/145 cluster is decreased in hepatitis B virus-associated hepatocellular carcinoma and may serve as a biomarker for tumorigenesis in patients with chronic hepatitis B

The aims of the present study were to identify the expression profile of microRNA (miR)‑143/145 in hepatitis B virus (HBV)‑associated hepatocellular carcinoma (HCC), explore its association with prognosis and investigate whether the serum miR‑143/145 expression levels may serve as a diagnostic indicator of HBV‑associated HCC. The microRNA (miRNA) chromatin immunoprecipitation dataset was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases, and analyzed using the Wilcoxon signed‑rank test. It was observed that the expression of miR‑143 and miR‑145 was decreased 1.5‑fold in HBV‑associated HCC samples compared with non‑tumor tissue in the TCGA and the GSE22058 datasets (P\u3c0.01). Using the reverse transcription‑quantitative polymerase chain reaction, it was further confirmed that miR‑143/145 and their host gene MIR143HG were downregulated in HBV‑associated HCC tissues compared with corresponding distal non‑tumor tissues. The lower level of miR‑143 and miR‑145 expression was associated with tumor differentiation, and may thus be responsible for a poor prognosis of patients with HBV‑associated HCC. The receiver‑operating characteristic (ROC) curves were used to explore the potential value of miR‑143 and miR‑145 as biomarkers for predicting HBV‑associated HCC tumorigenesis. In serum, miR‑143/145 were identified to be significantly decreased in patients with HBV‑associated HCC compared with negative control patients, and their associated areas under the ROC curves were calculated at 0.813 and 0.852 (P\u3c0.05), with each having a sensitivity and a specificity close to 0.80. These results indicated that the decreased expression of the miR‑143/145 cluster and their host gene MIR143HG in HBV‑associated HCC tissue was associated with prognosis, and each of these miRNAs may serve as a valuable diagnostic biomarker for predicting HBV‑associated HCC tumorigenesis

Pygopus 2 promotes kidney cancer OS-RC-2 cells proliferation and invasion in vitro and in vivo

AbstractObjectiveHuman Pygopus 2 (Pygo2) was recently discovered to be a component of the Wnt signaling pathway required for β-catenin/Tcf-mediated transcription. But the role of Pygo2 in malignant cell proliferation and invasion has not yet been determined.MethodsLentivirus-mediated small interfering RNA (siRNA) and vector-based overexpression were used to study the function of Pygo2 in OS-RC-2 cells. The resulted cells were subject to Western blotting assay, MTT assay, colony formation and cell invasion assays. Furthermore, renal cell carcinoma (RCC) models were established in BALB/c nude mice inoculated with OS-RC-2 cells. Immunohistochemistry (IHC) staining of matrix metalloproteinase-7 (MMP-7), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) was performed in tumor tissue.ResultsPygo2 gene was successful knocked down and overexpressed in RCC OS-RC-2 cells by using an shRNA and overexpressing vector, respectively. Overexpression of Pygo2 effectively promoted cell proliferation, colony formation and invasion in vitro. Knockdown of Pygo2 obviously inhibited xenograft tumor growth in nude mice. In addition, overexpression of Pygo2 increased the levels of MMP-7, MMP-9 and VEGF in the xenograft tumors.ConclusionPygo2 has a role in promoting cell proliferation, invasion and metastasis, and may regulate angiogenesis via the Wnt/β-catenin signaling pathway

Causal association of gastroesophageal reflux disease with obstructive sleep apnea and sleep-related phenotypes: a bidirectional two-sample Mendelian randomization study

BackgroundThe interactions and associations between obstructive sleep apnea (OSA), sleep-related phenotypes (SRPs), and gastroesophageal reflux disease (GERD) are complex, thus it is hard to explore the effect and direction of causalities.Study objectivesA bidirectional Mendelian randomization (MR) study was performed to explore causal associations of GERD with OSA and SRPs (including insomnia, morningness, sleep duration, ease of getting up, daytime napping, daytime dozing, and snoring).MethodsFirst, we gathered summary statistics from publicly available databases. Subsequently, we identified single-nucleotide polymorphisms without strong linkage (r2 ≤ 0.001) by referencing relevant genome-wide association studies that met genome-wide significance criteria. Our primary analysis relied on inverse variance weighted to estimate the causal relationship. To ensure the validity of our findings, we also conducted several sensitivity analyses. These included MR Pleiotropy RESidual Sum and Outlier to detect and correct for potential pleiotropic effects, MR-Egger to assess directional pleiotropy, and weighted median analysis to further evaluate heterogeneity and pleiotropy. For the initial MR analysis, when causality was indicated by the results, instrumental variables that were significantly linked to the aforementioned confounding factors were removed. We will re-analyze the data after excluding outcome-related single nucleotide polymorphisms to confirm that the results are still consistent with the previous results.ResultsGERD was found to increase the risk of OSA (OR = 1.53, 95% CI = 1.37–1.70, p = 5.3 × 10−15), insomnia (OR = 1.14, 95% CI = 1.10–1.19, p = 1.3 × 10−10), snoring (OR = 1.09, 95% CI = 1.04–1.13, p = 6.3 × 10−5) and less sleep duration (OR = 0.94, 95% CI = 0.91–0.97, p = 3.7 × 10−4). According to the reverse-direction analysis, there is an elevated risk of GERD associated with OSA (OR = 1.07, 95% CI = 1.02–1.12, p = 0.005), insomnia (OR = 1.95, 95% CI = 1.60–2.37, p = 1.92 × 10−11) and snoring (OR = 1.74, 95% CI = 1.37–2.21, p = 4.4 × 10−6).ConclusionGenetic susceptibility to GERD can elevate the likelihood of experiencing insomnia, snoring, and OSA, in addition to diminishing sleep duration. Conversely, a reverse MR analysis indicates that ameliorating any one of insomnia, snoring, or OSA can mitigate the risk of developing GERD

Original Article Splenosis in gastric fundus mimicking gastrointestinal stromal tumor: a report of two cases and review of the literature

Abstract: Splenosis refers to heterotopic autotransplantation and implantation of splenic tissue following splenic trauma or surgery. Splenosis in gastric fundus is rare and difficult to diagnose, since splenosis has similar manifestation with gastrointestinal stromal tumor (GIST) under routine endoscopy examination. In this report, we present two quite rare case of splenosis. Both of their pre-operative diagnose under endoscopic ultrasonography was considered as GIST. Finally, one in the abdominal cavity, adhering closely to the gastric fundus, measuring 20 mm × 15 mm, was resected by surgical operation, and one in the gastric fundus, measuring 20 mm × 20 mm, was resected by endoscopic surgery. The precise diagnosis of splenosis was distinct by post-operative histopathologic examination. In addition, we also made a mini review of previously published articles, in order to provide indication to solve future doubts in diagnosing and treating splenosis

The nucleus accumbens functional connectivity in patients with insomnia using resting-state fMRI

BackgroundThe aim of this study was to investigate the functional abnormalities between the nucleus accumbens (NAc) and the whole brain in individuals with Insomnia Disorder (ID) using resting-state functional magnetic resonance imaging (fMRI). Additionally, the study aimed to explore the underlying neural mechanisms of ID.MethodsWe enrolled 18 participants with ID and 16 normal controls (NC). Resting-state functional connectivity (FC) between the NAc and the whole brain voxels was calculated and compared between the two groups to identify differential brain region. Receiver operating characteristic (ROC) curve analysis was employed to assess the ability of differential features to distinguish between groups. Furthermore, Pearson correlation analysis was performed to examine the relationship between neurocognitive scores and differential features.ResultsThe ID group exhibited significantly reduced FC values in several brain regions, including the right supplementary motor area, the bilateral middle frontal gyrus, the bilateral median cingulate and paracingulate gyri and the left precuneus. The area under the curve (AUC) of the classification model based on FC in these brain regions was 83.3%. Additionally, the abnormal functional changes observed in ID patients were positively correlated with the Fatigue Severity Scale (R = 0.650, p = 0.004).ConclusionThese findings suggest that the NAc may play a crucial role in the diagnosis of ID and could serve as a potential imaging biomarker, providing insights into the underlying neural mechanisms of the disorder

Concentration effects in solid-state CD spectra of chiral atropisomeric compounds

Atropisomerism is one of the basic concepts in stereochemistry. Chiral crystals of stereochemically labile atropisomers that originated from Mirror Symmetry Breaking (MSB) can only be characterized by solid-state chiroptical techniques. Herein, solid-state circular dichroism and UV-Vis spectra of six atropisomeric compounds (most of them were obtained from MSB) have been studied. A concentration effect including a wavelength shift and inverse concentration-dependence has been found and preliminarily explained by the absorption flattening effect, scattering effect and the torsion in the molecular structures.National Natural Science Foundation of China[20973136, 20974028, 20732004]; Natural Science Foundation of Fujian Province[2010J01048

Expression of the microRNA-143/145 cluster is decreased in hepatitis B virus-associated hepatocellular carcinoma and may serve as a biomarker for tumorigenesis in patients with chronic hepatitis B

The aims of the present study were to identify the expression profile of microRNA (miR)‑143/145 in hepatitis B virus (HBV)‑associated hepatocellular carcinoma (HCC), explore its association with prognosis and investigate whether the serum miR‑143/145 expression levels may serve as a diagnostic indicator of HBV‑associated HCC. The microRNA (miRNA) chromatin immunoprecipitation dataset was obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus databases, and analyzed using the Wilcoxon signed‑rank test. It was observed that the expression of miR‑143 and miR‑145 was decreased 1.5‑fold in HBV‑associated HCC samples compared with non‑tumor tissue in the TCGA and the GSE22058 datasets (P\u3c0.01). Using the reverse transcription‑quantitative polymerase chain reaction, it was further confirmed that miR‑143/145 and their host gene MIR143HG were downregulated in HBV‑associated HCC tissues compared with corresponding distal non‑tumor tissues. The lower level of miR‑143 and miR‑145 expression was associated with tumor differentiation, and may thus be responsible for a poor prognosis of patients with HBV‑associated HCC. The receiver‑operating characteristic (ROC) curves were used to explore the potential value of miR‑143 and miR‑145 as biomarkers for predicting HBV‑associated HCC tumorigenesis. In serum, miR‑143/145 were identified to be significantly decreased in patients with HBV‑associated HCC compared with negative control patients, and their associated areas under the ROC curves were calculated at 0.813 and 0.852 (P\u3c0.05), with each having a sensitivity and a specificity close to 0.80. These results indicated that the decreased expression of the miR‑143/145 cluster and their host gene MIR143HG in HBV‑associated HCC tissue was associated with prognosis, and each of these miRNAs may serve as a valuable diagnostic biomarker for predicting HBV‑associated HCC tumorigenesis