Abstract
AIM: Deepening our understanding of the molecular mechanism of abdominal aortic aneurysm (AAA) progression will help set up novel avenues for therapeutic target identification. Our aim here was to unveil the mechanism function of STAT3 in AAA progression. METHODS: We investigated the functional role of STAT3 in AAA by evaluating vascular smooth muscle cell (VSMC) apoptosis and proliferation via terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting, 5-ethynyl-2´-deoxyuridine, and Cell Counting Kit-8 assays. The interplay of lncRNA-miRNA-mRNA was verified using the luciferase reporter assay and the RNA pull-down, RNA immunoprecipitation, and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction and western blot were utilized to quantitate the RNA and protein levels of the indicated molecules. RESULTS: Inhibition of STAT3 facilitated VSMC proliferation and repressed VSMC apoptosis. Moreover, It was demonstrated that small nucleolar RNA host gene 16 (SNHG16) sponged miR-106b-5p to release STAT3 from the inhibitory effect of miR-106b-5p. SNHG16 led to the upregulation of STAT3, and STAT3 was an upstream factor in the activation of SNHG16 transcription. Moreover, rescue experiments indicated that SNHG16 depended on STAT3 to regulate VSMC apoptosis and proliferation. In vivo assays showed that SNHG16 knockdown retarded the formation of AAA and upregulated STAT3 in vivo. CONCLUSIONS: We identified that SNHG16/miR-106b-5p/STAT3 formed a complex circuitry for the deterioration of AAA via regulating VSMCs, suggesting a possible target for the pathogenesis of AAA.