Recombinant Poliovirus type 1 Core protein P2A

Emodin is a Chinese herb-derived compound that exhibits a variety of pharmacological benefits. Although emodin has been shown to inhibit growth of cancer cells, its antineoplastic function is incompletely understood. CD155 is a member of poliovirus receptor-related (PRR) family of adhesion molecules; it is constitutively expressed on many tumor cell lines and tissues and has diverse functions. CD155 has been reported to mediate activation of T cells via CD226 or inhibition of T cells via T-cell immunoreceptor with Ig and ITIM domains (TIGIT). In addition, CD155 may play a critical role through non-immunological mechanisms in cancer. In this study, we tested the ability of emodin to modulate CD155 expression in cancer cells. We found that emodin significantly decreased the expression of CD155 in tumor cells and inhibited tumor cell proliferation and migration, and induced cell-cycle arrest at G2/M phase. The tumor inhibitory effects of emodin were lost with CD155 knockdown. Furthermore, emodin was used to treat mice bearing B16 melanoma. It was shown that emodin attenuated tumor growth accompanied by suppressing CD155 expression. Therefore, we propose that emodin could inhibit tumor growth, and the antineoplastic properties of emodin are at least partially CD155 dependent. Our study provides new insights into the mechanisms by which emodin inhibits tumor growth.

Translating the findings of genome wide association studies (GWAS) to new therapies requires identification of the relevant immunological contexts to interrogate for genetic effects. In one of the largest GWAS, more than 200 risk loci have been identified for Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears to be necessary for the development of Multiple Sclerosis (MS). Many MS risk loci are associated with altered gene expression in EBV infected B cells (LCLs). We have interrogated this immunological context to identify interaction between MS risk loci and EBV DNA copy number, intrinsic growth rate and EBV encoded miRNA expression. The EBV DNA copy number was associated with significantly more risk alleles for MS than for other diseases or traits. EBV miRNAs BART4-3p and BART3-5p were highly associated with EBV DNA copy number and MS risk loci. The poliovirus receptor (PVR) risk SNP was associated with EBV DNA copy number, PVR and miRNA expression. Targeting EBV miRNAs BART4-3p and BART3-5p, and the gene PVR, may provide therapeutic benefit in MS. This study also indicates how immunological context and risk loci interactions can be exploited to validate and develop novel therapeutic approaches.