Department of Vascular Surgery, Qingdao Municipal Hospital, Qingdao, China.
Department of Cardiovascular Surgery, Shengli Oilfield Central Hospital, Dongying, China.
ESC Heart Fail. 2022 Oct;9(5):2955-2966. doi: 10.1002/ehf2.13968. Epub 2022 Jun 21.
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.
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.
HOXA-AS2 up-regulates KIAA1522 through targeting miR-520d-3p/IGF2BP3 to drive VSMC growth in TAA.
长链非编码 RNA(lncRNA)最近被揭示介导胸主动脉瘤(TAA)中的平滑肌功能障碍。lncRNA HOXA-AS2 被提出参与多种疾病的调节。然而,其在 TAA 中的功能尚不清楚。本研究旨在揭示 HOXA-AS2 在涉及 TAA 形成的 VSMCs 中的作用和机制。
通过 RT-qPCR 或 Western blot 检测 RNA 或蛋白质表达水平。通过功能测定探索 HOXA-AS2 在 VSMCs 中的作用。通过机制测定分析 HOXA-AS2/miR-520d-3p/KIAA1522/IGF2BP3 之间的关系。HOXA-AS2 在 TAA 组织中表达水平显著升高,作为癌基因促进 VSMCs 的增殖,同时抑制细胞凋亡(图 1,**P < 0.01)。揭示 HOXA-AS2 与 miR-520d-3p 结合(图 2,*P < 0.05,**P < 0.01),进一步上调 KIAA1522 促进 VSMCs 的生长(图 3-4,*P < 0.05,**P < 0.01)。还发现 HOXA-AS2 募集 IGF2BP3 以稳定 KIAA1522 mRNA(图 5,**P < 0.01)。所有数据均以平均值±标准差表示。
HOXA-AS2 通过靶向 miR-520d-3p/IGF2BP3 上调 KIAA1522 驱动 TAA 中的 VSMC 生长。