Comprehensive analysis of REST corepressors (RCORs) in pan-cancer

REST corepressors (RCORs) are the core component of the LSD1/CoREST/HDACs transcriptional repressor complex, which have been revealed differently expressed in various cancers, but the therapeutic and prognostic mechanisms in cancer are still poorly understood. In this study, we analyzed expression, prognostic value, molecular subtypes, genetic alteration, immunotherapy response and drug sensitivity of RCORs in pan-cancer. Clinical correlation, stemness index, immune infiltration and regulatory networks of RCORs in hepatocellular carcinoma (HCC) were detected through TCGA and GSCA database. In-vitro experiments were conducted to explore the role of RCOR1 in HCC cells. The expression of RCORs varied among different cancers, and have prognostic values in several cancers. Cancer subtypes were categorized according to the expression of RCORs with clinical information. RCORs were significantly correlated with immunotherapy response, MSI, drug sensitivity and genetic alteration in pan-cancer. In HCC, RCORs were considered as potential predictor of stemness and also had association with immune infiltration. The ceRNA-TF-kinase regulatory networks of RCORs were constructed. Besides, RCOR1 acts as an oncogene in HCC and promotes the proliferation of HCC cells by inhibiting cell cycle arrest and cell apoptosis. Taken together, our study revealed the potential molecular mechanisms of RCORs in pan-cancer, offering a benchmark for disease-related research

A Mode-Sum Prescription for Vacuum Polarization in Even Dimensions

We present a mode-sum regularization prescription for computing the vacuum polarization of a scalar field in static spherically-symmetric black hole spacetimes in even dimensions. This is the first general and systematic approach to regularized vacuum polarization in higher even dimensions, building upon a previous scheme we developed for odd dimensions. Things are more complicated here since the even-dimensional propagator possesses logarithmic singularities which must be regularized. However, in spite of this complication, the regularization parameters can be computed in closed form in arbitrary even dimensions and for arbitrary metric function $f(r)$. As an explicit example of our method, we show plots for vacuum polarization of a massless scalar field in the Schwarzschild-Tangherlini spacetime for even $d=4,...,10$. However, the method presented applies straightforwardly to massive fields or to nonvacuum spacetimes.Comment: arXiv admin note: text overlap with arXiv:1609.0816

Hemolymphangioma of the chest wall: A rare case report

Hemolymphangioma is a rare, benign and non-invasive type of tumor. Only a few cases have been reported in the literature. In the present study, we report a case of hemolymphangioma growing on the left anterior chest wall of a 57-year-old woman. Physical and laboratory examinations were all normal. However, computed tomography (CT) revealed a mass. A CT-guided biopsy was performed, followed by a thoracoscopic resection and thoracotomy. The postoperative course of the patient was uneventful. Follow up of the patient is ongoing. The findings of this case report, however, showed the significance of complete excision versus minimally invasive surgery to reduce recurrence

MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer

Abstract Background Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation. Methods Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC. Results MiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC. Conclusion MiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient

Hepatoma-Derived Growth Factor-Related Protein-3 Is a Novel Angiogenic Factor

<div><p>Hepatoma-derived growth factor-related protein-3 (Hdgfrp3 or HRP-3) was recently reported as a neurotrophic factor and is upregulated in hepatocellular carcinoma to promote cancer cell survival. Here we identified HRP-3 as a new endothelial ligand and characterized its <i>in vitro</i> and <i>in vivo</i> functional roles and molecular signaling. We combined open reading frame phage display with multi-round <i>in vivo</i> binding selection to enrich retinal endothelial ligands, which were systematically identified by next generation DNA sequencing. One of the identified endothelial ligands was HRP-3. HRP-3 expression in the retina and brain was characterized by Western blot and immunohistochemistry. Cell proliferation assay showed that HRP-3 stimulated the growth of human umbilical vein endothelial cells (HUVECs). HRP-3 induced tube formation of HUVECs in culture. Wound healing assay indicated that HRP-3 promoted endothelial cell migration. HRP-3 was further confirmed for its <i>in vitro</i> angiogenic activity by spheroid sprouting assay. HRP-3 extrinsically activated the extracellular-signal-regulated kinase ½ (ERK1/2) pathway in endothelial cells. The angiogenic activity of HRP-3 was independently verified by mouse cornea pocket assay. Furthermore, <i>in vivo</i> Matrigel plug assay corroborated HRP-3 activity to promote new blood vessel formation. These results demonstrated that HRP-3 is a novel angiogenic factor.</p></div

HRP-3 induces endothelial cell sprouting and ERK activation.

<p>(A) Endothelial cell sprouts induced by HRP-3. HUVEC spheroids were embedded in fibrin gel and cultured in EBM-2 medium in the presence of HRP-3 (10 ng/ml), VEGF (2.5 ng/ml) or PBS for 48 h. Bar = 100 μm. (B) Quantification of endothelial cell sprouts. The average length of sprouts per spheroid was quantified as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127904#pone.0127904.s001" target="_blank">S1 Fig</a>. A total of 10 spheroids per group were quantified (n = 10). Data are mean ± s.e.m. in one representative experiment. **<i>P</i><0.01, *** <i>P</i><0.001, vs. control. (C) HRP-3 activates ERK pathway. HUVECs were starved in serum-free medium for 45 min, followed by incubation with HRP-3 or EGF (positive control) for 10 min. The cell lysate were analyzed by Western blot using antibody against ERK, phospho-ERK (pERK) or β-actin. Both experiments were validated three times with similar outcomes.</p