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Background Immunosuppressive receptor LILRB1 regulates tumors progression by transducing immune inhibitory signals via intracellular immunoreceptor tyrosine-based inhibitory motifs. However, its role in Hepatocellular Carcinoma (HCC) remains vague. Objective This study is aimed to disclose the association between LILRB1 and HCC. Methods Immunoblotting and qRT-PCR were employed to evaluate the level of LILRB1 in hepatocarcinoma cells. LILRB1-positive cells in tissue array were measured using immunohistochemistry staining. The relation among LILRB1, SHP1 and SHP2 and survival rates were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine database. Results LILRB1 was robustly reduced in hepatocarcinoma cells compared to normal cells. Clinically, LILRB1 was significantly higher in 49 of 75 (65%) paired paracarcinoma tissues than that in paired HCC samples. 48 of 75 (64%) HCC subjects in tissue microarray showed low level of LILRB1, compared to 25 of 75 (33%) in paired-adjacent tissues. Oncomine database and GEPIA analysis confirmed that LILRB1 was lower in HCC than normal tissues. Additionally, lowLILRB1 had a significant association with clinicopathological characteristics and Disease Free Survival, but no association with Overall Survival in HCC patients. Mechanismly, positive correlation between LILRB1 and SHP1, but not SHP2 was observed in HCC. Conclusions LILRB1 possibly plays an antitumor effect in hepatocarcinoma cells by integrating SHP1, providing evidence that LILRB1 might be involved in the pathologic progression of HCC.

Wuke Zhang,1 Pengtao Jiang,2,3 Pengcheng Tong,1 Ting Xu,1 Ruizhi Yuan,3 Liuting Diao1 1Business School, Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2International Affairs Office, NingboTech University, Ningbo, Zhejiang Province, People’s Republic of China; 3Business School, University of Nottingham Ningbo China, Ningbo, Zhejiang Province, People’s Republic of ChinaCorrespondence: Liuting Diao, Business School, Ningbo University, 818 Fenghua Road, Ningbo, 315211, People’s Republic of China, Tel +86 15168164056, Email diaoliuting@nbu.edu.cnPurpose: This study aims to explore the influence of industry leaders’ behavior on common enterprise leaders’ decisions in enterprise clustering by recognizing top executives’ cognitive processes of brains.Methods: Twenty-one real top executives from twelve textile enterprises were recruited in the lab experiment, and decisions about whether entering an industrial zone under two conditions of following an industry leader or a common enterprise were designed as the experiment task. Throughout the formal experimental task, participants’ electroencephalograms were recorded.Results: The behavioral results preliminarily proved the effect of industry leaders’ behaviors on the real top executives’ decisions in common enterprises: participants had a higher acceptance rate with a shorter reaction time in the condition of following an industry leader rather than that in the condition of following a common enterprise. Event-related potential results indicated that choices of following an industry leader led to a more positive perception of emotional valence (reflected by a smaller P2 amplitude) and better evaluation categorization and greater decision confidence (reflected by a larger late positive potential amplitude) than choices of following a common enterprise.Conclusion: Top executives from common enterprises tend to evaluate industry leaders’ behaviors better than other common enterprises’ behaviors, and they tend to make a similar business decision to keep their enterprises consistent with these industry leaders.Keywords: leading effect, business decision, ERPs, P2, LPP

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid progenitor and precursor cells at different stages of differentiation, which play an important role in tumor immunosuppression. Glioma is the most common and deadliest primary malignant tumor of the brain, and ample evidence supports key contributions of MDSCs to the immunosuppressive tumor microenvironment, which is a key factor stimulating glioma progression. In this review, we summarize the source and characterization of MDSCs, discuss their immunosuppressive functions, and current approaches that target MDSCs for tumor control. Overall, the review provides insights into the roles of MDSC immunosuppression in the glioma microenvironment and suggests that MDSC control is a powerful cellular therapeutic target for currently incurable glioma tumors.

Objective— Long noncoding RNAs (lncRNA) represent a growing class of noncoding genes with diverse cellular functions. We previously reported on SENCR , an lncRNA that seems to support the vascular smooth muscle cell (VSMC) contractile phenotype. However, information about the VSMC-specific lncRNAs regulated by myocardin (MYOCD)/serum response factor, the master switch for VSMC differentiation, is unknown. Approach and Results— To define novel lncRNAs with functions related to VSMC differentiation, we performed RNA sequencing in human coronary artery SMCs that overexpress MYOCD. Several novel lncRNAs showed altered expression with MYOCD overexpression and one, named MYOcardin-induced Smooth muscle LncRNA, Inducer of Differentiation ( MYOSLID ), was activated by MYOCD and selectively expressed in VSMCs. MYOSLID was a direct transcriptional target of both MYOCD/serum response factor and transforming growth factor-β/SMAD pathways. Functional studies revealed that MYOSLID promotes VSMC differentiation and inhibits VSMC proliferation. MYOSLID showed reduced expression in failed human arteriovenous fistula samples compared with healthy veins. Although MYOSLID did not affect gene expression of transcription factors, such as serum response factor and MYOCD, its depletion in VSMCs disrupted actin stress fiber formation and blocked nuclear translocation of MYOCD-related transcription factor A (MKL1). Finally, loss of MYOSLID abrogated transforming growth factor-β1–induced SMAD2 phosphorylation. Conclusions— We have demonstrated that MYOSLID , the first human VSMC-selective and serum response factor/CArG-dependent lncRNA, is a novel modulator in amplifying the VSMC differentiation program, likely through feed-forward actions of both MKL1 and transforming growth factor-β/SMAD pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, but the pathogenesis of NAFLD is not fully clear. The aim of this study was to determine whether autophagy plays a role in the pathogenesis of NAFLD. We found that the levels of autophagy were elevated in hepatoma cells upon exposure to free fatty acids, as confirmed by the increase in the number of autophagosomes. However, exposure of hepatoma cells to H2O2 and TNF-α, two typical "second hit" factors, increased the initiation of autophagy but inhibited the autophagic flux. The inhibition of autophagy sensitized cells to pro-apoptotic stimuli. Taken together, our results suggest that autophagy acts as a protective mechanism in the pathogenesis of NAFLD and that impairment of autophagy might induce more severe lesions of the liver. These findings will be a benefit to the understanding of the pathogenesis of NAFLD and might suggest a strategy for the prevention and cure of NAFLD.

Background: Breast cancer (BCa) is a genetically heterogeneous disease and many genes contributing to BCa risk remain to be identified. Genome-Wide Association Studies (GWAS) and subsequent fine-mapping studies (>50) have strongly implicated genetic alterations at the CCDC170/C6ORF97-ESR1 locus (6q25.1) as being associated with the risk of BCa. ESR1, encoding the estrogen receptor, might be a more obvious candidate for influencing risk. Surprisingly, our analysis using genome-wide differential allele-specific expression (DASE), an indicator for BCa susceptibility, suggested that the genetic alterations of CCDC170, but not ESR1, accounts for GWAS-associated BCa risk at this locus. CCDC170 is a coiled-coiled domain-containing protein of poorly understood function. BCa-specific truncation and missense mutations in CCDC170 also have been detected, with the truncations being implicated in driving Luminal B subtype BCa. Together these findings demonstrate that the CCDC170 gene is involved in BCa, but the underlying molecular mechanisms for its role in tumorigenesis are unknown. Experimental designs and results: By using the approaches of confocal microscopy and cell imaging analysis, here we report for the first time that CCDC170 is associated with the Golgi apparatus and perinuclear microtubules (MTs), and support a role for CCDC170 in the Golgi-associated microtubule network. We have shown that overexpression of CCDC170 triggers Golgi reorganization and stabilizes Golgi-associated MTs, accompanied by dramatically increased acetylation of α-tubulin that is driven by the acetyltransferase ATAT1. The Golgi-associated MT network has been proposed to regulate cell polarity and migration. In support of this concept, we have shown that CRISPR knockout increases, and overexpression of CCDC170 decreases, BCa directional cell migration in vitro. We also found that the BCa-specific truncations result in mislocalization of CCDC170 and/or diminished stability of Golgi-associated MTs. Lastly, we identified candidate CCDC170 functional binding partners (e.g. MAP4) that are consistent with its localization and proposed function. These partners may serve to mediate the acetylation and stabilization of MTs. Conclusions: Taken together, our findings demonstrate that CCDC170 plays an essential role in Golgi-associated MT organization and stabilization, and provide a mechanism for how perturbations in CCDC170 could alter Golgi-mediated cell polarity, and thereby drive BCa and other abnormalities. This work was partially supported by the Susan G. Komen for the Cure (KG100274), NCI (CA186853), and Eileen Stein Jacoby Fund. Citation Format: Pengtao Jiang, Yueran Li, Andrey Poleshko, Valentina Medvedeva, Natalia Baulina, Yongchao Zhang, Yan Zhou, Carolyn M. Slater, Trinity Pellegrin, Jason Wasserman, Michael Lindy, Mary Daly, Richard A. Katz, Xiaowei Chen. The breast cancer gene CCDC170 regulates the Golgi-associated microtubule network and directional cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2017-1884

The role played by cytokines, other than interferon (IFN)-α, in the differentiation and function of dendritic cells (DCs) in systemic lupus erythematosus (SLE), remains unclear. Serum interleukin-10 (IL-10) levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) + IL-4 + tumor necrosis factor (TNF)-α. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen (HLA)-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs.