Department of General Surgery, Xinxiang Central Hospital, Xinxiang, 453000 Henan, China.
Weifang Yidu Central Hospital, Weifang, 261000 Shangdong, China.
Biomed Pharmacother. 2020 Sep;129:109904. doi: 10.1016/j.biopha.2020.109904. Epub 2020 Jun 16.
Long noncoding RNAs (LncRNAs) are involved in multiple processes of human malignancy, and emerge as crucial molecules in RNA biology. However, the function of lncRNAs has not been well illustrated in abdominal aortic aneurysm (AAA). In this research, the effects of dysregulated ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) or ladybird homeobox 2 (LBX2) on vascular smooth muscle cell (VSMC) biological processes were surveyed via cell counting kit-8 (CCK-8), methyl thiazolyl tetrazolium (MTT), terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and caspase-3 activity assays. LBX2-AS1 and LBX2 both possessed pro-apoptosis and anti-proliferation functions in AAA. Mechanically, the regulation role of LBX2-AS1 on miR-4685-5p or that of miR-4685-5p on LBX2 was investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the competing endogenous RNA (ceRNA) network was confirmed by luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. LBX2-AS1 sequestered miR-4685-5p to release LBX2 expression via ceRNA mechanism. Further, LBX2 could act as a transcriptional activator of LBX2-AS1. A positive feedback loop was formed by LBX2-AS1, miR-4685-5p and LBX2, deteriorating AAA formation and progression. To sum up, our data suggested that LBX2-AS1, miR-4685-5p and LBX2 constituted a positive feedback loop in promoting AAA development, implying a potential usage of LBX2-AS1/miR-4685-5p/LBX2 axis in AAA management.
长链非编码 RNA（lncRNAs）参与人类恶性肿瘤的多个过程，是 RNA 生物学中重要的分子。然而，lncRNAs 在腹主动脉瘤（AAA）中的作用尚未得到充分说明。在这项研究中，通过细胞计数试剂盒-8（CCK-8）、甲基噻唑基四唑（MTT）、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）和 caspase-3 活性测定，研究了失调的瓢虫同源盒 2 反义 RNA 1（LBX2-AS1）或瓢虫同源盒 2（LBX2）对血管平滑肌细胞（VSMC）生物学过程的影响。LBX2-AS1 和 LBX2 在 AAA 中均具有促凋亡和抗增殖作用。在机制上，通过定量实时聚合酶链反应（qRT-PCR）研究了 LBX2-AS1 对 miR-4685-5p 的调控作用或 miR-4685-5p 对 LBX2 的调控作用。此外，通过荧光素酶报告、RNA 下拉和 RNA 免疫沉淀（RIP）测定证实了竞争内源性 RNA（ceRNA）网络。LBX2-AS1 通过 ceRNA 机制结合 miR-4685-5p 释放 LBX2 表达。此外，LBX2 可以作为 LBX2-AS1 的转录激活剂。通过 LBX2-AS1、miR-4685-5p 和 LBX2 形成正反馈环，加剧 AAA 的形成和进展。总之，我们的数据表明，LBX2-AS1、miR-4685-5p 和 LBX2 构成了促进 AAA 发展的正反馈环，提示 LBX2-AS1/miR-4685-5p/LBX2 轴在 AAA 管理中的潜在用途。
