Department of Vascular Surgery, Minhang Hospital, Fudan University, No. 39 Xinling Road, Minhang District, 201199, Shanghai, China.
Inflammation. 2020 Oct;43(5):1620-1633. doi: 10.1007/s10753-020-01237-6.
Over the past few decades, long noncoding RNAs (lncRNAs) have been widely accepted to be involved in various diseases, and smooth muscle enriched long noncoding RNA (SMILR) was reported to participate in the proliferation of vascular smooth muscle cells (VSMCs). Nevertheless, the molecular mechanisms of SMILR in atherosclerosis (AS) have not been fully explored. In this study, VSMCs and human mononuclear cells (U937) treated with oxidized low-density lipoprotein (ox-LDL) were used as cell models of AS. We found that the expression of SMILR was upregulated in the serum of AS patients and ox-LDL-induced AS cell models. SMILR knockdown inhibited cell proliferation while increasing cell apoptosis in the AS cell models. In addition, SMILR acted as a sponge for miR-10b-3p, and miR-10b-3p counteracted SMILR-mediated regulation of AS. Moreover, we confirmed that miR-10b-3p could bind with KLF5, and SMILR regulated KLF5 expression by competitively binding miR-10b-3p. Furthermore, miR-10b-3p modulated cell proliferation and apoptosis in AS by targeting KLF5. Finally, miR-10b-3p regulated AS progression in vivo by targeting KLF5. Overall, our study demonstrated that SMILR participated in the progression of AS by targeting the miR-10b-3p/KLF5 axis, which may provide some clues for future studies of AS.
在过去的几十年中，长链非编码 RNA（lncRNA）被广泛认为参与各种疾病，平滑肌丰富的长链非编码 RNA（SMILR）被报道参与血管平滑肌细胞（VSMCs）的增殖。然而，SMILR 在动脉粥样硬化（AS）中的分子机制尚未完全阐明。在本研究中，使用氧化低密度脂蛋白（ox-LDL）处理的 VSMCs 和人单核细胞（U937）作为 AS 的细胞模型。我们发现，SMILR 在 AS 患者的血清和 ox-LDL 诱导的 AS 细胞模型中的表达上调。SMILR 敲低抑制了 AS 细胞模型中的细胞增殖，同时增加了细胞凋亡。此外，SMILR 作为 miR-10b-3p 的海绵，miR-10b-3p 抵消了 SMILR 对 AS 的调节作用。此外，我们证实 miR-10b-3p 可以与 KLF5 结合，并且 SMILR 通过竞争性结合 miR-10b-3p 调节 KLF5 表达。此外，miR-10b-3p 通过靶向 KLF5 调节 AS 中的细胞增殖和凋亡。最后，miR-10b-3p 通过靶向 KLF5 在体内调节 AS 的进展。总之，我们的研究表明，SMILR 通过靶向 miR-10b-3p/KLF5 轴参与 AS 的进展，这可能为 AS 的未来研究提供一些线索。
