Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown. In this study, we demonstrated that SiO2 NP induced the expression of follistatin (FST), a stress responsive gene, in mouse lung tissue as well as in human lung epithelial cells (A549). The levels of Ac-H3(K9/18) and H3K4me2, two active gene markers, at FST promoter region were significantly increased during SiO2 NP treatment. The induction of FST transcription was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2), as evidenced by the decreased FST expression in Nrf2-deficient cells and the direct binding of Nrf2 to FST promoter region. Down-regulation of FST promoted SiO2 NP-induced apoptosis both in cultured cells and in mouse lung tissue. Furthermore, knockdown of FST increased while overexpression of FST decreased the expression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxygen species (ROS). Taken together, these findings demonstrated a protective role of FST in SiO2 NP-induced oxidative stress and shed light on the interaction between SiO2 NPs and biological systems.
Previous studies have indicated an association between the genetic variant in pre-miR-27a rs895819 with A->G transition and cancer risk; however, the results remain inconsistent and somehow conflicting in different cancers. Therefore, to obtain a more reliable conclusion, we performed an update meta-analysis by searching PubMed database or other databases. Odds ratio (ORs) and 95% confidence interval (CIs) were calculated to evaluate cancer risk. A total of 34 case-control studies involving 15,388 cases and 18,704 controls were included. The results showed that rs895819 was associated with an increased cancer risk (GG vs. AA/AG: OR = 1.15, 95% CI = 1.02–1.29). Furthermore, stratification analyses revealed an association of rs895819 with increased cancer risk among Asians (GG vs. AA: OR = 1.17, 95% CI = 1.01–1.36; GG vs. AA/AG: OR = 1.18, 95% CI = 1.03–1.35), but not Caucasians. Interestingly, the [G] allele of rs895819 was significantly associated with decreased risk of breast cancer (G vs. A: OR = 0.91, 95% CI = 0.86–0.97). However, rs895819 was associated with increased risk of colorectal cancer (GG vs. AA: OR = 1.56, 95% CI = 1.31–1.85; GG vs. AA/AG: OR = 1.53, 95% CI = 1.30–1.79; G vs. A: OR = 1.19, 95% CI = 1.09–1.30) and lung cancer (GG vs. AA/AG: OR = 1.43, 95% CI = 1.00–2.04). In addition, no association was found between rs895819 and risk of gastric cancer or esophageal cancer. In conclusion, our findings suggest distinct effects of rs895819 on risk of different cancers, and future well-designed studies with large samples are required to further validate our results.
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