School of Basic Medical Sciences, Northwest Minzu University Health Science Center, No. 1, XibeiXincun Chengguan District, Lanzhou City, Gansu Province, 730030, People's Republic of China.
Department of intensive care unit, Gansu Provincial Corps Hospital of Chinese People's Armed Police Force, Lanzhou City, Gansu Province, 730050, People's Republic of China.
Mol Med. 2020 Jul 22;26(1):74. doi: 10.1186/s10020-020-00200-3.
Studies have demonstrated that long noncoding RNAs (lncRNAs) have essential impacts on the development of atherosclerosis (AS). This study aimed to identify the role and functional mechanism of lncRNA CASC2 in the development and migration of vascular smooth muscle cells (VSMCs).
The serum of 40 pairs of AS patients and healthy volunteers were collected and the expression of CASC2 was evaluated. qRT-PCR and western blotting were carried out to examine the expression levels of at mRNA and protein level, repectively. Cell proliferation assay, colony formation assay, transwell migration assay, dual-luciferase reporter assay, and wound healing assay were conducted to evaluate cell proliferation, colony formation, migration, transcription, targeting, and self-restoration.
The expression levels of CASC2 were decreased, while the expression levels of miR-532-3p were elevated in AS patient samples and VSMCs. Overexpression of CASC2 inhibited the proliferation and migration of VSMCs and enhanced cell apoptosis. CASC2 inhibited the expression of miR-532-3p, and inversely upregulated the expression of PAPD5, which was a target of miR-532-3p. In addition, knockdown of miR-532-3p-mimic and PAPD5 could attenuate the impact of overexpression of CASC2 on proliferation, migration, and apoptosis in ox-LDL-VSMCs.
CASC2 suppressed cell reproduction and promoted cell apoptosis by regulating the miR-532-3p/PAPD5 axis in ox-LDL-mediated VSMCs. This might be important for AS therapeutics.
研究表明，长链非编码 RNA（lncRNA）对动脉粥样硬化（AS）的发展有重要影响。本研究旨在鉴定 lncRNA CASC2 在血管平滑肌细胞（VSMCs）发育和迁移中的作用和功能机制。
收集 40 对 AS 患者和健康志愿者的血清，评估 CASC2 的表达。qRT-PCR 和 Western blot 分别用于检测 mRNA 和蛋白水平的表达。细胞增殖试验、集落形成试验、Transwell 迁移试验、双荧光素酶报告试验和划痕愈合试验用于评估细胞增殖、集落形成、迁移、转录、靶向和自我修复。
CASC2 的表达水平降低，而 miR-532-3p 在 AS 患者样本和 VSMCs 中的表达水平升高。CASC2 的过表达抑制了 VSMCs 的增殖和迁移，并增强了细胞凋亡。CASC2 抑制了 miR-532-3p 的表达，同时上调了 PAPD5 的表达，PAPD5 是 miR-532-3p 的靶标。此外，miR-532-3p 模拟物和 PAPD5 的敲低可以减弱过表达 CASC2 对 ox-LDL-VSMCs 增殖、迁移和凋亡的影响。
CASC2 通过调节 ox-LDL 介导的 VSMCs 中的 miR-532-3p/PAPD5 轴抑制细胞增殖并促进细胞凋亡。这可能对 AS 的治疗具有重要意义。
