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.

中文翻译：

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SMILR通过海绵化miR-10b-3p调节KLF5表达来加剧动脉粥样硬化的进展。

在过去的几十年中，长的非编码RNA（lncRNA）被广泛认为与多种疾病有关，据报道，富含平滑肌的长非编码RNA（SMILR）参与了血管平滑肌细胞（VSMC）的增殖。然而，SMILR在动脉粥样硬化（AS）中的分子机制尚未得到充分探索。在这项研究中，VSMC和经氧化的低密度脂蛋白（ox-LDL）处理的人单核细胞（U937）被用作AS的细胞模型。我们发现SMILR的表达在AS患者的血清和ox-LDL诱导的AS细胞模型中被上调。SMILR组合物抑制细胞增殖，同时在AS细胞模型中增加细胞凋亡。此外，SMILR充当miR-10b-3p的海绵，而miR-10b-3p则抵消了SMILR介导的AS调节。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来调节KLF5的表达。此外，miR-10b-3p通过靶向KLF5来调节AS中的细胞增殖和凋亡。最后，miR-10b-3p通过靶向KLF5体内调节AS进展。总体而言，我们的研究表明SMILR通过靶向miR-10b-3p / KLF5轴参与了AS的发展，这可能为AS的未来研究提供一些线索。