Effects of Common Polymorphism rs11614913 in Hsa-miR-196a2 on Lung Cancer Risk

<div><p>Background</p><p>Emerging evidence suggests that single nucleotide polymorphisms (SNPs) in microRNA-coding genes may participate in the pathogenesis of lung cancer by altering the expression of tumor-related microRNAs. Several studies were investigated in recent years to evaluate the association between hsa-miR-196a2 rs11614913 polymorphism and increased/decreased lung cancer risk. In the present study, we performed a meta-analysis to systematically summarize the possible association.</p><p>Methodology/Principal Findings</p><p>We performed a meta-analysis of 4 case-control studies that included 2219 lung-cancer cases and 2232 cancer-free controls. We evaluated the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In the overall analysis, it was found that the rs11614913 polymorphism significantly elevated the risk of lung cancer (CC versus (vs.) TT OR = 1.26, 95% CI 1.07–1.49, P = 0.007; CC/CT vs. TT: OR = 1.13, 95% CI 0.98–1.29, P = 0.007; C vs. T: OR = 1.12, 95% CI 1.03–1.22, P = 0.008). In the subgroup analysis by ethnicity, statistically significantly increased cancer risk was found among Asians (CC vs. TT: OR = 1.30, 95% CI 1.10–1.54, P = 0.003; CT vs. TT: OR = 1.16, 95% CI 1.01–1.34, P = 0.039; CC vs. CT/TT: OR = 1.21, 95% CI 1.04–1.41, P = 0.012; C vs. T: OR = 1.14, 95% CI 1.05–1.25, P = 0.002). For Europeans, a significant association with lung cancer risk was found in recessive model (CC vs. CT/TT: OR = 0.63, 95% CI 0.40–0.98, P = 0.040). No publication bias was found in this study.</p><p>Conclusions/Significance</p><p>Our meta-analysis suggests that the rs11614913 polymorphism is significant associated with the increased risk of lung cancer, especially in Asians. Besides, the C allele of rs11614913 polymorphism may contribute to increased lung cancer risk.</p></div

Forest plots of the association between lung cancer risk and hsa-miR-196a2 rs11614913 polymorphism under homozygote comparison (CC vs. TT).

<p>OR: odds ratio; CI: confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses. The squares and horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study specific weight. The diamond represents the pooled OR and 95% CI.</p

Characteristics of eligible studies included in the meta-analysis.

*<p>Hardy-Weinberg equilibrium (HWE) was evaluated using the goodness-of-fit chi-square test. P values were presented. P<0.05 was considered representative of a departure from HWE. PCR-RFLP was polymerase chain reaction-restriction fragment length polymorphism. PCR-HRMA was PCR-high-resolution melting analysis.</p

Begg’s funnel plot for publication bias test.

<p>OR: odds ratio; Log OR is plotted versus standard error of Log OR for each enrolled study. Horizontal line stands for mean effect size. Each circle point represents a separate study for the indicated association between hsa-miR-196a2 rs11614913 polymorphism and lung cancer risk by homozygote comparison (CC vs. TT).</p

Flow diagram of study identification with criteria for inclusion and exclusion in the meta-analysis.

<p>Flow diagram of study identification with criteria for inclusion and exclusion in the meta-analysis.</p

Meta-analysis of hsa-miR-196a2 rs11614913 polymorphism and lung cancer risk.

<p>N, number of comparisons; OR, odds ratio; CI, confidence interval; vs., versus; CC vs. TT: Homozygote comparison; CT vs. TT: Heterozygote comparison; CC/CT vs. TT: Dominant model; CC vs. CT/TT: Recessive model; C vs. T: Allele comparison; R, random effect model; F, fixed effect model; Random effect model was chosen when P-value <0.10 and/or I²>50% for heterogeneity test; otherwise fixed effect model was used.</p

Forest plots of the association between lung cancer risk and hsa-miR-196a2 rs11614913 polymorphism under homozygote comparison (CC vs. TT) in different ethnicity.

<p>OR: odds ratio; CI: confidence interval; I-squared, measure to quantify the degree of heterogeneity in meta-analyses. The squares and horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the study specific weight. The diamond represents the pooled OR and 95% CI.</p

Strong Lewis Base Ga₄B₂O₉: Ga–O Connectivity Enhanced Basicity and Its Applications in the Strecker Reaction and Catalytic Conversion of <i>n</i>‑Propanol

Heterogeneous solid base catalysis is valuable and promising in chemical industry, however it is insufficiently developed compared to solid acid catalysis due to the lack of satisfied solid base catalysts. To gain the strong basicity, the previous strategy was to basify oxides with alkaline metals to create surficial vacancies or defects, which suffers from the instability under catalytic conditions. Monocomponent basic oxides like MgO are literally stable but deficient in electron-withdrawing ability. Here we prove that a special connectivity of atoms could enhance the Lewis basicity of oxygen in monocomponent solids exemplified by Ga₄B₂O₉. The structure-induced basicity is from the μ₃-O linked exclusively to five-coordinated Ga³⁺. Ga₄B₂O₉ behaved as a durable catalyst with a high yield of 81% in the base-catalyzed synthesis of α-aminonitriles by Strecker reaction. In addition, several monocomponent solid bases were evaluated in the Strecker reaction, and Ga₄B₂O₉ has the largest amount of strong base centers (23.1 μmol/g) and the highest catalytic efficiency. Ga₄B₂O₉ is also applicable in high-temperature solid–gas catalysis, for example, Ga₄B₂O₉ catalyzed efficiently the dehydrogenation of <i>n</i>-propanol, resulting in a high selectivity to propanal (79%). In contrast, the comparison gallium borate, Ga-PKU-1, which is a Brönsted acid, preferred to catalyze the dehydration process to obtain propylene with a selectivity of 94%

Effects of different treatments on blood counts and routine biochemical parameters.

<p>(Compared to the normal saline group: **P<0.01;*P<0.05)</p><p>(Compared to the As₂O₃ injection and albumin-bound As₂O₃ groups: △△P<0.01)</p><p>Effects of different treatments on blood counts and routine biochemical parameters.</p

Bladder weights and inhibitory rates observed in 4 BALB/c-nu mice (%).

<p>(Compared with the normal saline group: **P<0.01)</p><p>Bladder weights and inhibitory rates observed in 4 BALB/c-nu mice (%).</p