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HOXA 簇反义 RNA2 通过 microRNA-520d-3p 和胰岛素样生长因子 2 mRNA 结合蛋白 3 上调 KIAA1522 表达,促进胸主动脉瘤血管平滑肌细胞的生长。

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.

机构信息

Department of Vascular Surgery, Qingdao Municipal Hospital, Qingdao, China.

Department of Cardiovascular Surgery, Shengli Oilfield Central Hospital, Dongying, China.

出版信息

ESC Heart Fail. 2022 Oct;9(5):2955-2966. doi: 10.1002/ehf2.13968. Epub 2022 Jun 21.

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.

摘要

目的

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。

方法和结果

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。

结论

HOXA-AS2 通过靶向 miR-520d-3p/IGF2BP3 上调 KIAA1522 驱动 TAA 中的 VSMC 生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d9/9715842/774f12cd0902/EHF2-9-2955-g001.jpg

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