Objective. Fibroblast-like synoviocytes (FLS) are a major component of the hyperplastic synovial pannus that aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Cyr61 (CCN1) is a product of a growth factor-inducible immediate early gene and is involved in cell adhesion, proliferation, and differentiation. However, the role that Cyr61 plays in FLS proliferation has remained undetermined. The aim of this study was to identify the role of Cyr61 in regulating the proliferation of FLS derived from patients with RA. Methods. Expression of Cyr61 in synovial tissue (ST) and in FLS was

Objective: Despite several clinicopathological factors being integrated as prognostic biomarkers, the individual variants and risk stratification have not been fully elucidated in lower grade glioma (LGG). With the prevalence of gene expression profiling in LGG, and based on the critical role of the immune microenvironment, the aim of our study was to develop an immune-related signature for risk stratification and prognosis prediction in LGG. Methods: RNA-sequencing data from The Cancer Genome Atlas (TCGA), Genome Tissue Expression (GTEx), and Chinese Glioma Genome Atlas (CGGA) were used. Immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). Univariate, multivariate cox regression, and Lasso regression were employed to identify differentially expressed immune-related genes (DEGs) and establish the signature. A nomogram was constructed, and its performance was evaluated by Harrell's concordance index (C-index), receiver operating characteristic (ROC), and calibration curves. Relationships between the risk score and tumor-infiltrating immune cell abundances were evaluated using CIBERSORTx and TIMER. Results: Noted, 277 immune-related DEGs were identified. Consecutively, 6 immune genes (CANX, HSPA1B, KLRC2, PSMC6, RFXAP, and TAP1) were identified as risk signature and Kaplan-Meier curve, ROC curve, and risk plot verified its performance in TCGA and CGGA datasets. Univariate and multivariate Cox regression indicated that the risk group was an independent predictor in primary LGG. The prognostic signature showed fair accuracy for 3-and 5-year overall survival in both internal (TCGA) and external (CGGA) validation cohorts. However, predictive performance was poor in the recurrent LGG cohort. The CIBERSORTx algorithm revealed that naïve CD4 + T cells were significant higher in low-risk group. Conversely, the infiltration levels of

Background Chemo-resistance is one of the major challenges in the therapy of small cell lung cancer (SCLC). Multiple mechanisms are thought to be involved in chemo-resistance during SCLC treatment, but unfortunately, these mechanisms have not been well elucidated. Herein, we investigated the role of miRNA in the resistance of SCLC cells to doxorubicin (Dox). Methods MiRNA microarray analysis revealed that several miRNAs, including miR-7-5p, were specifically decreased in Dox-resistant SCLC cells (H69AR) compared to parental cells (H69). The expression level of miR-7-5p was confirmed by qRT-PCR in Dox-resistant cells (H69AR and H446AR cells) and their parental cells. Bioinformatic analysis indicated that poly ADP-ribose polymerase 1 (PARP1) is a direct target of miR-7-5p. The binding sites of miR-7-5p in the PARP1 3′ UTR were verified by luciferase reporter and Western blot assays. To investigate the role of miR-7-5p in the chemo-resistance of SCLC cells to doxorubicin, mimic or inhibitor of miR-7-5p was transfected into SCLC cells, and the effect of miR-7-5p on homologous recombination (HR) repair was analyzed by HR reporter assays. Furthermore, the expression of HR repair factors (Rad51 and BRCA1) induced by doxorubicin was detected by Western blot and immunofluorescent staining in H446AR cells transfected with miR-7-5p mimic. Results The expression level of miR-7-5p was remarkably reduced ( -fold) in Dox-resistant SCLC cells (H69AR and H446AR cells) compared with that in parental cells (H69 and H446 cells). Poly ADP-ribose polymerase 1 (PARP1) is a direct target of miR-7-5p, and PARP1 expression was downregulated by miR-7-5p. MiR-7-5p impeded Dox-induced HR repair by inhibiting the expression of HR repair factors (Rad51 and BRCA1) that resulted in resensitizing SCLC cells to doxorubicin. Conclusions Our findings provide evidence that miR-7-5p targets PARP1 to exert its suppressive effects on HR repair, indicating that the alteration of the expression of miR-7-5p may be a promising strategy for overcoming chemo-resistance in SCLC therapy. Electronic supplementary material The online version of this article (10.1186/s12885-019-5798-7) contains supplementary material, which is available to authorized users.

B7 homolog 4 (B7H4) is considered a negative regulator of immune responses, but the immunoregulatory role of B7H4 in the tumor microenvironment is not clear. Here, we assessed B7H4 expression cell types in human breast cancer tissues and addressed its potential mechanisms in the CD8 T cell immune response. The results from flow cytometry and immunohistochemistry demonstrated that B7H4 was highly expressed in 26 out of 30 (86.7%) breast invasive ductal carcinomas, and B7H4 surface expression on tumor cells was inversely correlated with CD8 T lymphocytes infiltration (p < 0.0001). In vivo, B7H4-overexpressing tumor cells showed enhanced tumor growth in immunocompetent mice with impaired CD8 T cell infiltration of the tumor. Further investigation showed that activation and expansion of CD8 T cells within the lymph nodes were suppressed in B7H4-overexpessing tumor-bearing mice. An in vitro killing assay showed that the cytotoxicity of CD8 T cells was inhibited in B7H4-overexpressing tumor cells. These findings suggest that B7H4 in tumor cells is a negative regulator of CD8 T cell activation, expansion and cytotoxicity, indicating that tumor cell-associated B7H4 might be a target for T cell-based cancer immunotherapy. Keywords B7 homolog 4 • Tumor microenvironment • T cell • Immune suppression • Adoptive transfer Abbreviations B7H4 B7 homolog 4 CFSE Carboxyfluorescein diacetate succinimidyl ester CTL Cytotoxic T lymphocyte FCM Flow cytometry IHC Immunohistochemistry IDC Invasive ductal carcinomas PBMC Peripheral blood mononuclear cell TCR T cell receptor TAM Tumor associated macrophage TIL Tumor infiltrating lymphocyte * Qiuyu Zhang