Long non-coding RNA (lncRNA) H19 is involved in tumor development, progression, and metastasis. This case-control study assessed the association between H19 genetic variants and susceptibility to gastric cancer (GC) in a Chinese Han population. We genotyped four lncRNA H19 single nucleotide polymorphisms (SNPs) (rs217727 C > T, rs2839698 C > T, rs3741216 A > T, rs3741219 T > C) in 500 GC patients and 500 healthy controls. Carriers of variant rs217727T and rs2839698T alleles showed increased GC risk (P = 0.008 and 0.011, respectively). Compared with the common genotype, CT + TT rs217727 and CT + TT rs2839698 genotypes were associated with significantly increased GC risk (P = 0.040, adjusted odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.01–1.71; P = 0.033, adjusted OR = 1.31, 95% CI = 1.02–1.69, respectively). Further stratified analyses revealed that the association between GC risk and variant genotypes of rs217727 was more profound in younger individuals (≤59 years) and non-smokers, while the association between risk and the rare rs2839698 genotype persisted in men and rural subjects. rs2839698 CT and TT genotypes were also associated with higher serum H19 mRNA levels compared with the CC genotype. These findings suggest that lncRNA H19 SNPs may contribute to susceptibility to GC.

In contrast to normal differentiated cells that depend on aerobicoxidation for energy production, cancer cells use aerobic glycolysis as the main source (Warburg's effect). The M2 splice isoform of pyruvate kinase (PKM2) is the key regulator for the aerobic glycolysis, high expression of PKM2 contributes to the aerobic glycolysis, promotes the growth of tumors. In the present study, we found that PKM2 was highly expressed in gastric cancer (GC) tissues and had a strongly inverse correlation with the expression of microRNA-let-7a (miR-let-7a). Furthermore, we found that the overexpression of miR-let-7a markedly suppressed the proliferation, migration, and invasion of GC cells by down-regulating the expression of PKM2. MicroRNAs (miRNAs) are important regulators play key roles in tumorigenesis and tumor progression. Although previous reports showed that let-7 family members act as tumor suppressors in many cancers. The specific regulatory mechanism of miR-let-7a to PKM2 in gastric cancer is still unclear. In this study, we revealed that miR-let-7a function as the antitumor and gene regulatory effects of PKM2 in GC cells.

Species richness patterns and endemism on the large-scale play a significant role in biogeography and biodiversity conservation. This study aimed to explore the diversity centers and endemic areas of a large cantharid genus Lycocerus, so as to test whether the hypothesis of montane and island systems biodiversity in previous studies was supported. In this study, a comprehensive species’ geographical database on the global scale consisting of 4,227 records for 324 Lycocerus species was compiled and analyzed. Species richness pattern was mapped into a grid-based map with a spatial resolution of 1° × 1° fishnet. An unbalanced pattern was identified, and it showed that the centers of species richness of Lycocerus were situated in Eastern Himalayas, Hengduan Mountains, Eastern Sichuan Mountains, Taiwan, and Japan. Further analyses based on two approaches, including parsimony analysis of endemicity (PAE) and endemicity analysis (EA), were applied to detect areas of endemism (AOEs) at three different grid sizes (1°, 1.5°, and 2°). Finally, a total of nine AOEs were detected, including five montane areas (Himalayan areas, Hengduan Mountains, South edge of China, Eastern China Mountains, and Eastern Sichuan Mountains), three islands (Taiwan Island, Japan, and Korean Peninsula), and one plateau (Shan Plateau), which were generally consistent with the species richness pattern. The results verify that montane and island systems have an essential role in promoting the formation of diversity centers and AOEs because of their complex topography, varied habitat and geological events.

Abstract. The integrality of low molecular weight protein (LMP)2/LMP7 function plays an important role in the processing of GC cell antigens. The purpose of the present hospital-based case-control study was to estimate the effect of polymorphisms in the LMP2 and LMP7 genes on the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to distinguish the Arg to His substitution at codon 60 of LMP2 (LMP2-60) and the Gln to Lys substitution at codon 145 of LMP7 (LMP7-145) in 502 gastric cancer patients and 502 age and gender-matched cancer-free control individuals. The Lys allele of the LMP7-145 variant was more frequent in GC patients compared with control individuals [P=0.004; adjusted odds ratio (OR), 1.39; 95% confidence interval (CI), 1.11-1.74]. The Gln/Lys and Lys/Lys genotypes increased the risk of GC compared with the Gln/Gln genotype (P=0.049 and P=0.041, respectively; adjusted OR, 1.32 and 2.13, respectively; 95% CI, 1.00-1.73 and 1.03-4.39, respectively). Compared with the Gln/Gln genotype, the LMP7-145 Gln/Lys and Lys/Lys variants of the LMP7 gene were also associated with increased susceptibility to GC (P=0.017; adjusted OR, 1.38; 95% CI, 1.06-1.80). Haplotype analysis revealed that the LMP2 (Arg)-LMP7 (Lys) haplotype was associated with increased risk of GC (P=0.013, adjusted OR=1.34, 95% CI=1.06-1.70). Stratified analysis revealed that the association between the risk of GC and the variant genotypes of LMP7-145 was stronger in older individuals (>59 years), males and non-smokers. However, no association between the LMP2-60 polymorphism and the risk of GC was observed. The present results suggest that the LMP7-145 genetic variant contributes to increased susceptibility to GC, and the Lys allele is an independent risk factor for GC.

Tissue differentiation-inducing non-protein coding RNA (TINCR) is required for normal epidermal differentiation. TINCR is also strongly overexpressed in human gastric cancer (GC) and contributes to carcinogenesis and tumor progression. However, the association between TINCR polymorphisms and the risk of any diseases, such as GC, remains unknown. In the present study, the tag single nucleotide polymorphisms rs8113645, rs2288947, rs8105637, and rs12610531 were analyzed in 602 patients with GC and 602 age- and sex-matched controls. Polymorphisms were genotyped using TaqMan technology. Carriers of variant rs8113645 and rs2288947 alleles indicated reduced risks of GC (p = 0.003 and 0.037, respectively). A allele genotypes of rs8113645 and G allele genotypes of rs2288947 (rs8113645 GA and AA; rs2288947 AG and GG) were also significantly associated with decreased GC risk (p < 0.05). Stratification analysis displayed that the correlations between GC risk and variant genotypes of both rs8113645 and rs2288947were more evident in younger individuals, men, nonsmokers, and individuals from rural areas. We also demonstrated that rs8113645 GA+AA genotype carriers had lower TINCR mRNA expression levels compared with common genotype in both normal and GC tissues (p < 0.05). These results suggest that long non-coding RNA TINCR polymorphisms may be implicated in GC development.

More and more evidence reveals that noncoding RNA miR-34b/c and tumor suppressor gene TP-53 independently, and/or jointly, play crucial roles in carcinogenesis. The purpose of the present hospital-based case-control study was to investigate the association between the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of gastric cancer. Two polymorphisms were genotyped in 419 gastric cancer patients and 402 age- and sex-matched cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism analysis. The CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype and T allele (CC vs. TT: P = 0.006, adjusted odds ratio (OR) = 0.53, 95 % confidence interval (95 % CI) = 0.34-0.83; C vs. T: P = 0.005, adjusted OR = 0.75, 95 % CI = 0.61-0.92). Compared with individuals with the wild-type TT genotype, subjects with the variant genotypes (CT + CC) had a significantly decreased risk of gastric cancer (P = 0.047, adjusted OR = 0.75, 95 % CI = 0.57-0.99). Stratified analysis showed that the association between the risk of gastric cancer and the variant genotypes of miR-34b/c was more profound among men. However, no overall association was found between the TP53 Arg72Pro polymorphism and gastric cancer risk. In the combined analysis, no effects of the interaction of miR-34b/c rs4938723 and TP53Arg72Pro on gastric cancer risk were observed. Our findings indicate that the miR-34b/c rs4938723 CT/CC genotypes may be associated with a decreased risk of gastric cancer and the C allele may be a protective factor in gastric cancer.

Tripartite motif 59 (TRIM59) is a novel oncogenic driver in gastric cancer (GC) that is implicated in disease progression as well as dismal survival. Genetic variants in peculiar gene are likely candidates for conferring hereditary susceptibility. The role of TRIM59 polymorphism in predicting the risk of malignant diseases and its relevance to TRIM59 expression have not been discussed. Using a HapMap tagSNPs approach, we screened three tag TRIM59 single nucleotide polymorphisms (SNPs) (rs1141023G>A, rs7629A>G, rs11706810T>C) which were genotyped in 602 GC patients and 868 healthy controls. Our study provided convincing result that carries of variant rs1141023A allele markedly increased GC risk (P=0.006). In comparison with the GG homozygotes, the variant GA heterozygotes demonstrated 1.50-fold elevated risk of GC (p=0.014, 95% confidence interval [CI] = 1.09–2.08). Subjects who carried the (GA+AA) genotypes of rs1141023 were associated with remarkable increased GC risk compared with the common genotype (P = 0.013, adjusted OR = 1.50, 95% CI = 1.09–2.05). Further stratified analyses displayed that the relationship between mutant genotype of rs1141023 and GC risk was more profound in male individuals. Intriguingly, there is no significant distinction of TRIM59 mRNA expression between rs1141023GA genotype and GG genotype in 44 normal gastric tissues. Taken together, our results suggest that rs1141023 polymorphism contributes to increased predisposition to GC and thus may be responsible for predicting early GC.

PurposeDisheveled-binding antagonist of beta-catenin 1 (DACT1) is involved in tumorigenesis through influencing cell apoptosis and proliferation. We aimed to investigate the effect of three tag single-nucleotide polymorphisms (SNPs) in DACT1 (rs863091 C>T, rs17832998 C>T, and rs167481 C>T) on the occurrence of gastric cancer (GC), their association with specific clinical characteristics, and consideration of the functional relevance of GC-related SNPs.Subjects and methodsIn this hospital-based case–control study, the genotypes were acquired using the TaqMan-MGB method consisting of 602 cases and 602 controls. DACT1 messenger RNA level was evaluated in 76 paired tumoral and normal tissues using quantitative reverse transcription–polymerase chain reaction. Logistic regression was used to evaluate the associations among the DACT1 SNPs and GC.ResultsWe found a significant association between the variant genotypes of rs863091 and decreased risk of GC (TT vs CC: P=0.009, adjusted odds ratio =0.34, 95% confidence interval =0.15–0.77; CT + TT vs CC: P=0.030, adjusted odds ratio =0.74, 95% confidence interval =0.57–0.97). In further stratified analyses, rs863091 variant genotypes were associated with a reduced risk of GC in younger individuals (<60 years) and males. No overall significant association with GC risk was observed in SNP rs17832998 or rs167481. Additionally, we assessed DACT1 messenger RNA levels in GC and found that DACT1 expressions of individuals carrying CT and TT genotypes were much higher than those with CC genotype.ConclusionOur findings suggest that the DACT1 rs863091 C>T polymorphism may be associated with a decreased risk of GC in the Chinese Han population and influence DACT1 expression.