Aims Recently, long non‐coding RNAs (lncRNAs) have been revealed to mediate smooth muscle dysfunction in thoracic aortic aneurysm (TAA). LncRNA HOXA‐AS2 has been proposed to engage in the regulation of diverse diseases. However, its function in TAA remains unknown. This study aimed to reveal the role and mechanism of HOXA‐AS2 in VSMCs which were implicated in TAA formation. Methods and results RT‐qPCR or western blot was performed to detect RNA or protein expression levels. The role of HOXA‐AS2 in VSMCs was explored by functional assays. The relationship among HOXA‐AS2/miR‐520d‐3p/KIAA1522/IGF2BP3 was analysed via mechanism assays. HOXA‐AS2 was detected to have significantly high expression in TAA tissues and function as an oncogene to promote proliferation of VSMCs, while inhibiting cell apoptosis (Figure 1, **P < 0.01). HOXA‐AS2 was unveiled to bind with miR‐520d‐3p (Figure 2, *P < 0.05, **P < 0.01) and further up‐regulate KIAA1522 to facilitate the growth of VSMCs (Figure 3–4, *P < 0.05, **P < 0.01). HOXA‐AS2 was also found to recruit IGF2BP3 to stabilize KIAA1522 mRNA (Figure 5, **P < 0.01). All data were displayed as mean ± standard deviation. Conclusions HOXA‐AS2 up‐regulates KIAA1522 through targeting miR‐520d‐3p/IGF2BP3 to drive VSMC growth in TAA.

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