Molecular epidemiological studies suggest that microRNA polymorphisms may be associated with an increased risk of coronary heart disease (CHD). However, the results of these studies were inconsistent and inconclusive. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between microRNA polymorphisms and CHD risk. PubMed, Embase, CNKI and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were applied to assess the association between microRNA-146a rs2910164, microRNA-196a2 rs11614913, microRNA-499 rs3746444 and microRNA-149 rs71428439 polymorphisms and CHD susceptibility. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. A total of thirteen related studies involving 8,120 patients and 8,364 controls were analyzed. Significant associations between microRNA-146a rs2910164 polymorphism and CHD risk were observed in the total population, as well as in subgroup analysis. For microRNA-196a2 rs11614913 and microRNA-499 rs3746444, similarly increased risks were also found. In addition, no significant association was detected between microRNA-149 rs71428439 polymorphism and CHD risk. In conclusion, our meta-analyses suggest that microRNA polymorphisms may be associated with increased risk of CHD development.
HOTAIR, a well-known long non-coding RNA, is involved in carcinogenesis and progression of multiple cancers. Molecular epidemiological studies suggest that HOTAIR polymorphisms may be associated with cancer susceptibility, but the results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on the associations between HOTAIR polymorphisms and cancer risk for the first time. PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. Odds ratios (ORs) with 95% confidence interval (CI) were applied to assess the association between HOTAIR rs920778 C>T, rs4759314 A>G, rs7958904 G>C, and rs1899663 G>T polymorphisms and cancer susceptibility. Analyses were conducted to detect heterogeneity, sensitivity, and publication bias in order to measure the robustness of our findings. Overall, 13 related studies involving 7,151 patients and 8,740 control samples were analyzed. Significant associations between the HOTAIR rs920778 polymorphism and cancer risk were observed (T vs C: OR =1.33, 95% CI =1.17–1.53; TT vs TC + CC: OR =1.55, 95% CI =1.21–2.00; TC + TT vs CC: OR =1.33, 95% CI =1.11–1.59; TT vs CC: OR =2.02, 95% CI =1.31–3.10) in the total population, as well as in subgroup analyses. For rs4759314 A>G polymorphism, a similarly increased risk was found in the gastric cancer group. However, significant decreases in cancer risk were observed both in the overall population and colorectal cancer group for rs7958904 G>C polymorphism. In addition, no significant association was detected between rs1899663 G>T polymorphism and cancer susceptibility. In conclusion, our meta-analyses suggest that HOTAIR polymorphisms may be associated with the risk of cancer development.
Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.
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