Benzene, a recognized carcinogen, is utilized in synthesizing various chemicals. Epidemiological studies have established a positive correlation between benzene exposure and increased incidences of abnormal menstruation and dysmenorrhea. This exposure might also pose risks to the fetal hematopoietic system. However, the precise molecular mechanisms underlying these effects are not fully understood. In this study, a chronic benzene exposure model was established through dynamic inhalation. We assessed the autophagy levels in mouse ovarian granulosa cells and human ovarian granulosa cells treated with 1,4-benzoquinone using molecular biology techniques such as qPCR, Western blot, and transmission electron microscopy (TEM), etc. The experimental results show that Benzene-exposed mice exhibited autophagy, a reduced number of ovarian granulosa cells, and vacuolar lesions in the fallopian tubes. Cell-based experiments demonstrated that benzene exposure significantly upregulated SNHG15 expression in human ovarian granulosa cells ( P < 0.05). The upregulation of SNHG15 enhanced FOXO3 expression via the miR-3143/FOXO3 axis, which in turn increased the transcription of autophagy-related proteins such as Atg5 ( P < 0.05), ultimately leading to excessive autophagy in granulosa cells and ovarian dysfunction. Benzene and its metabolite benzoquinone increase autophagy in ovarian granulosa cells. The lncRNA SNHG15 regulates this autophagy induced by benzene exposure through sponge-like binding to miR-3143/FOXO3, thus impairing ovarian function. Inhibiting SNHG15, miR-3143, and FOXO3 expression markedly reduced autophagy in granulosa cells and ameliorated ovarian dysfunction resulting from benzene exposure. These results suggest that the ceRNA axis involving SNHG15 may be a potential clinical therapeutic target.
Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.
危险品化学品经营许可证（带存储）