TLR3 gene polymorphisms in cancer: a systematic review and meta-analysis / 癌症

<p><b>INTRODUCTION</b>Recent studies examining the association of Toll-like receptor 3 (TLR3) gene polymorphisms with the risk of developing various types of cancer have reported conflicting results. Clarifying this association could advance our knowledge of the influence of TLR3 single nucleotide polymorphisms (SNPs) on cancer risk.</p><p><b>METHODS</b>We systematically reviewed studies that focused on a collection of 12 SNPs located in the TLR3 gene and the details by which these SNPs influenced cancer risk. Additionally, 14 case-control studies comprising a total of 7997 cases of cancer and 8699 controls were included in a meta-analysis of 4 highly studied SNPs (rs3775290, rs3775291, rs3775292, and rs5743312).</p><p><b>RESULTS</b>The variant TLR3 genotype rs5743312 (C9948T, intron 3, C>T) was significantly associated with an increased cancer risk as compared with the wild-type allele (odds ratio [OR]=1.11, 95% confidence interval [CI]=1.00-1.24, P=0.047). No such association was observed with other TLR3 SNPs. In the stratified analysis, the rs3775290 (C13766T, C>T) variant genotype was found to be significantly associated with an increased cancer risk in Asian populations. Additionally, the rs3775291 (G13909A, G>A) variant genotype was significantly associated with an increased cancer risk in Asians, subgroup with hospital-based controls, and subgroup with a small sample size.</p><p><b>CONCLUSION</b>After data integration, our findings suggest that the TLR3 rs5743312 polymorphism may contribute to an increased cancer risk.</p>

The effect of iNOS gene expression inhibited by RNA inference on the pancreas islet apoptosis and function in rats / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of iNOS gene on cell apoptosis and insulin secretion of pancreas islet in rats by RNA inference (RNAi).</p><p><b>METHODS</b>Islets obtained from thirty Wistar rats were randomly divided into five groups, and siRNA oligo was purchased from Genepharma in Shanghai. The cultured islets were transfected with iNOS siRNA, and then were divided into five groups. Islet cultured only was taken as blank control group, and cultured with TNF-alpha + IL-1 beta as cytokine group. Islet transfected with negative or iNOS siRNA were taken as negative transfection control group or RNAi group, while that transfected with iNOS siRNA and cultured with TNF-alpha + IL-1 beta as RNAi + cytokine group. Expression of iNOS mRNA was evaluated by RT-PCR and iNOS protein was evaluated by Western blot to detect the effect of RNAi. The expression of apoptosis correlated gene, Bax, Fas were analyzed, and the apoptotic cells were identified by TUNEL method meanwhile. Insulin secretion index assay the function of the islets.</p><p><b>RESULTS</b>500 - 600 IEQ islets could be extracted from every rat. RNAi attenuated the expression of iNOS and restrained the synthesis of iNOS protein.With treatment of cytokines IL-1 beta and TNF-alpha, the level of iNOS increased remarkably, the expression of Bax and Fas ascended distinctly, and insulin secretion index decreased strikingly. While, the expression of apoptosis gene and amount of apoptotic cells descended in group of RNAi + cytokine, and insulin secretion index were satisfying.</p><p><b>CONCLUSION</b>The apoptosis from cytokines to islets mediated by iNOS could be suppressed by RNAi, which leaded to favorable function and survival of islets.</p>