MicroRNAs (miRNAs) function as gene regulator and they participate in diverse biological pathways. Common single nucleotide polymorphisms (SNPs) in pre-microRNAs may change their property through altering miRNAs expression and/or maturation. We conducted a pilot study to test whether SNPs in pre-microRNAs were associated with cervical squamous cell carcinoma (CSCC). Genotypes of three SNPs in pre-miRNAs (hsa-miR-196a2 rs11614913 C/T, hsa-miR-499 rs3746444 A/G, and hsa-miR-146a rs2910164 G/C) in 226 CSCC patients and 309 control subjects were determined with the use of PCR-restriction fragment length polymorphism (RFLP) assay. Significantly increased CSCC risks were found to be associated with G allele of rs3746444 and G allele of rs2910164 (P = 0.017, OR = 1.454, and P = 0.016, OR = 1.355, respectively). Increased CSCC risks were associated with them in different genetic model (P = 0.0004, OR = 1.98 for rs3746444 in an overdominant model, and P = 0.024, OR = 2.10 for rs2910164 in a codominant model, respectively). Results of stratified analyses revealed that rs2910164 is associated with tumor differentiation and lymph node status (P = 0.043, OR = 2.08, and a borderline P = 0.057, OR = 0.41, respectively). No association between rs11614913 and CSCC risk was observed. The present study provides evidence that rs3746444 and rs2910164 are associated with CSCC, indicating that common genetic polymorphisms in pre-microRNAs contribute to the pathogenesis of CSCC.

Interleukin-17 (IL-17) is a proinflammatory cytokine that is associated with inflammation, autoimmune disorders, and even tumors. Previous studies revealed that a large group of human malignant tumors have abnormally high IL-17 expression. In the present study, we analyzed two single-nucleotide polymorphisms (SNPs) in the IL17A (rs2275913) and IL17F (rs763780) in 311 cervical cancer patients and 463 controls using TaqMan assays. Our results indicated that the frequencies of AA genotype and A allele of rs2275913 were significantly different between the cervical cancer patients and controls (P = 0.008, OR = 1.32, 95% CI, 1.07–1.62). Stratified analyses revealed that the polymorphism of rs2275913 was also associated with positive peritumor intravascular cancer emboli and high clinical stage. The genotype and allele frequencies of rs763780 did not show any difference between patients and controls or relate to patient clinical characteristics. Collectively, these findings suggested that IL17 gene polymorphism rs2275913 was associated with the susceptibility as well as positive peritumor intravascular cancer emboli and high clinical stage of cervical cancer in Chinese women.

T he human gastrointestinal tract is populated with at least 100 trillion bacteria that provide their host with dietary metabolites. Extensive studies have demonstrated that human gut microbiota affect energy balance, gut permeability, serum lipopolysaccharides levels, and metabolic inflammation associated with obesity and diabetes mellitus.1 Subjects with obesity and type 2 diabetes mellitus are characterized by altered gut microbiota, inflammation, and gut barrier disruption. In addition, the population of beneficial gut bacteria has been found to be reduced in animal models of metabolic syndrome. For instance, the abundance of a beneficial gut bacterium, Akkermansia muciniphila (A muciniphila), is significantly lower in the genetically obese ob/ob mice or mice fed a high-fat diet compared with their lean littermates. Increased colonization of A muciniphila has also been found to be capable of reversing high-fat diet-induced metabolic disorders.2 In contrast, disease-promoting gut bacteria induce metabolic disorders. For instance, a strain of the Enterobacter cloacae, B29, isolated from a morbidly obese human, induced obesity and insulin resistance in a rodent model, and the severity of disease was found to be closely related to the lipid content in the diet. 3A muciniphila is a mucin-degrading bacterium that resides in the mucus layer of intestine, and it abundantly colonizes in this nutrient-rich environment. 4 Oral administration of live A muciniphila has been shown to prevent diet-induced obesity by altering adipose tissue metabolism and gut permeability without affecting food intake.2 However, the regulatory effect of A muciniphila on host lipid metabolism, particularly on hepatic lipid signaling and lipoprotein metabolism, is unexplored.© 2016 American Heart Association, Inc. Objective-Akkermansia muciniphila (A muciniphila) is a mucin-degrading bacterium that resides in the mucus layer whose abundance inversely correlates with body weight and the development of diabetes mellitus in mice and humans. The objective of this study was to explore the regulatory effect of A muciniphila on host lipoprotein metabolism, insulin sensitivity, and hepatic metabolic inflammation. Approach and Results-By establishing a novel mouse model that colonized the A muciniphila in the gastrointestinal tract of the cAMP-responsive binding protein H (CREBH)-deficient mouse and in vivo chylomicron assay, we found that increased colonization of A muciniphila in the gastrointestinal tract of wild-type mice protected mice from an acute fat load-induced hyperlipidemia compared with vehicle-treated mice. A muciniphila administration also significantly ameliorated chronic hypertriglyceridemia, improved insulin sensitivity, and prevented overproduction of postprandial chylomicrons in CREBH-null mice. Mechanistic studies revealed that increased A muciniphila colonization induced expression of low-density lipoprotein receptors and apolipoprotein E in the hepatocytes of CREBH-null mice, which facilitated the uptake of intermediate-density...

No abstract