LncRNA SNHG14 drives angiotensin-induced abdominal aortic aneurysm progression by regulating autophagy via the miR-27b-3p/Wnt/β-catenin/c-Myc axis

Abdominal aortic aneurysm (AAA) is a global health concern associated with high mortality. It has been reported that long noncoding RNAs (lncRNAs) are involved in the development of AAA. In this study, our objective was to investigate the roles of lncRNA small nucleolar RNA host gene 14 (SNHG14) and the associated mechanisms in the development of AAA. An AAA mouse model was established by administering angiotensin II (Ang II). The expression of SNHG14 in abdominal aortic tissues was evaluated using in situ hybridization and reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). The incidence of AAA and the maximal aortic diameter were analyzed. Hematoxylin-eosin staining, Elastica van Gieson staining, western blotting, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and immunofluorescence staining were performed to assess the in vivo effects of SNHG14. Human arterial smooth muscle cells (HASMCs) were treated with Ang II to simulate AAA-like conditions in vitro. RT-qPCR, flow cytometry, western blotting, and immunofluorescence staining were carried out. The molecular mechanisms of SNHG14 were also investigated through luciferase reporter assays, western blotting, and chromatin immunoprecipitation assays. Our findings revealed that knockdown of SNHG14 inhibited the development of AAA and alleviated Ang II-induced pathological alterations and Apoptosis in mice. Additionally, silencing of SNHG14 promoted Autophagy in aortic tissues. For in vitro analysis, downregulation of SNHG14 inhibited Apoptosis of HASMCs and promoted Autophagy in vitro. Mechanistically, SNHG14 targeted miR-27b-3p, and inhibition of miR-27b-3p counteracted the protective effects of SNHG14 knockdown. Additionally, SNHG14 activated the Wnt/β-catenin signaling pathway. Moreover, c-Myc bound to the SNHG14 promoter and activated its transcription. In conclusion, our study demonstrates that overexpression of the lncRNA SNHG14 might exacerbate the formation of AAA by promoting Apoptosis of HASMCs and inhibiting Autophagy through the miR-27b-3p/Wnt/β-catenin/c-Myc axis.

Abdominal aortic aneurysm; Autophagy; Wnt/β-catenin; c-Myc; lncRNA SNHG14; miR-27b-3p.