长链非编码 RNA UCA1 通过海绵吸附 miR-26a 调控血管平滑肌细胞的迁移和增殖。
LncRNA UCA1 sponges miR-26a to regulate the migration and proliferation of vascular smooth muscle cells.
机构信息
Department of Cardiology, China Water Resource and Hyropower, No. 13th, Engineering Bureau Hospital, Dezhou, Shandong 253000, China.
Department of Respiratory Medicine, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China.
出版信息
Gene. 2018 Oct 5;673:159-166. doi: 10.1016/j.gene.2018.06.031. Epub 2018 Jun 13.
BACKGROUND
Recent studies have shown that the long non-coding RNA urothelial carcinoma-associated (UCA1) plays a key role in cardiovascular injury. However, the potential biological role of UCA1 in progression of atherosclerosis (AS) remains unclear. The aim of the present study is to identify the regulation of lncRNA UCA1 on atherosclerosis-related vascular dysfunction via miR-26a targeting phosphatase and tensin homolog (PTEN), and investigate the underlying mechanisms in the development of atherosclerosis.
METHODS
The proliferation and migration were detected using CCK-8 assay, Wound healing assay and Transwell assay. The expression of miR-26a and its target gene in vascular smooth muscle cells was detected by qRT-PCR, the complementary binging of miRNA and lncRNA was verified by luciferase assays. PTEN was predicted to be the target of miR-26a and the prediction was verified by luciferase assays.
RESULTS
Expression of miR-26a was up-regulated in ox-LDL (50 mg/l) induced vascular smooth muscle cell (VSMCs), and overexpression of miR-26a inhibited PTEN expression and promoted PCNA α-SMA and SM22-α expression (qRT-PCR and WB).
CONCLUSION
The expression of UCA1 antagonized the effect of miR-26a on the downregulation of its target PETN and contraction phenotype. This study reveals that lncRNA UCA1 act as an endogenous sponge of miR-26a and downregulates miR-26a expression levels, and thereby relieving the inhibition of its target gene PTEN and alleviates VSMCs proliferation against atherosclerosis.
背景
最近的研究表明，长链非编码 RNA 尿路上皮癌相关（UCA1）在心血管损伤中发挥关键作用。然而，UCA1 在动脉粥样硬化（AS）进展中的潜在生物学作用尚不清楚。本研究旨在通过 miR-26a 靶向磷酸酶和张力蛋白同源物（PTEN）来确定 lncRNA UCA1 对动脉粥样硬化相关血管功能障碍的调节作用，并研究其在动脉粥样硬化发生发展中的潜在机制。
方法
采用 CCK-8 法、划痕愈合实验和 Transwell 实验检测细胞增殖和迁移。qRT-PCR 检测血管平滑肌细胞中 miR-26a 及其靶基因的表达，荧光素酶实验验证 miRNA 与 lncRNA 的互补结合。预测 PTEN 是 miR-26a 的靶基因，并通过荧光素酶实验验证。
结果
ox-LDL（50mg/L）诱导的血管平滑肌细胞（VSMCs）中 miR-26a 的表达上调，过表达 miR-26a 抑制 PTEN 表达，促进 PCNA、α-SMA 和 SM22-α 表达（qRT-PCR 和 WB）。
结论
UCA1 的表达拮抗了 miR-26a 对其靶基因 PETN 的下调作用和收缩表型。本研究表明，lncRNA UCA1 作为 miR-26a 的内源性海绵，下调 miR-26a 的表达水平，从而缓解其靶基因 PTEN 的抑制作用，缓解 VSMCs 增殖对动脉粥样硬化的作用。
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