HOXA cluster antisense RNA 2 elevates KIAA1522 expression through microRNA‐520d‐3p and insulin like growth factor 2 mRNA binding protein 3 to promote the growth of vascular smooth muscle cells in thoracic aortic aneurysm

Abstract

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.

The Role of Long Noncoding RNAs in Vascular Smooth Muscle Cell Phenotype and the Pathogenesis of Cardiovascular and Cerebrovascular Aneurysms

“…For instance, the HOXA-AS2 upregulates KIAA1522 by targeting miR-520d-3p/IGF2BP3 to drive VSMC growth in TAA. 128 NEAT1 induces VSMC apoptosis, which promotes TAA formation by targeting the miR-324-5p/RAN axis. 113 H19 suppressed proliferation, accelerated apoptosis, and caused ECM degradation between VSMCs.…”

Spotlight on HOX cluster‑embedded antisense lncRNAs in cardiovascular diseases (Review)

“…Recently, HOXA-AS2 was found to be highly expressed in thoracic aortic aneurysm (TAA) tissues. HOXA-AS2 upregulates the expression of NHS like 3 by targeting miR-520d-3p/IGF2BP3 to drive VSMC growth in TAA ( 60 ). Therefore, HOX lncRNAs are important regulators of VSMC proliferation and migration.…”

Role of HOXA1-4 in the development of genetic and malignant diseases

“…Moreover, HOXA-AS2 acts as a sponge for miR-520c-3p and miR-106a to regulate TGFBR2/RELA and SCN3A, respectively, thereby enhancing tumor progression in BC [ 169 , 170 ]. Additionally, HOXA-AS2 is implicated in the development and progression of various other cancers, including CC [ 171 ], papillary thyroid cancer[ 172 ], type I endometrial carcinoma [ 173 ], NPC [ 174 ], osteosarcoma [ 175 ], NSCLC [ 176 ], bladder cancer (BCa) [ 177 ], and thoracic aortic aneurysm [ 178 ]. In these cases, HOXA-AS2 modulates different miRNA-related pathways, such as miR-509-3p/BTN3A1, miR-15a-5p/HOXA3, miRNA-302c-3p/ZFX, miR-519/HIF-1α/PD-L1, miR-124-3p/E2F3, miR-216a-5p, miR-125b/Smad2, and miR-520d-3p/KIAA1522/IGF2BP3, to promote tumor progression (Table 3 and Fig.…”