Department of Vascular Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Gynecology and Obstetrics, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Int J Mol Med. 2021 Feb;47(2):741-750. doi: 10.3892/ijmm.2020.4821. Epub 2020 Dec 16.
Long non‑coding RNAs (lncRNAs) have been discovered to participate in the progression of various types of disease and may be a promising biomarker for atherosclerosis (AS). The present study aimed to investigate the regulatory mechanisms of the lncRNA, small nucleolar RNA host gene 7‑003 (SNHG7‑003), on the proliferation, migration and invasion of vascular smooth muscle cells (VSMCs). VSMCs were first stimulated with oxidized low‑density lipoprotein (ox‑LDL) to simulate AS in a high fat environment. The expression levels of SNHG7‑003, microRNA (miRNA/miR)‑1306‑5p and sirtuin 7 (SIRT7) were analyzed by reverse transcription‑quantitative PCR and the effects of each of these factors on VSMC proliferation, migration and invasion were determined by Cell Counting Kit‑8, wound healing and Transwell assays, respectively. Western blot analysis was also used to analyze the protein expression levels of α‑smooth muscle actin (α‑SMA), matrix metalloproteinase (MMP)2 and MMP9. The interactions between SNHG7‑003 or SIRT7 and miR‑1306‑5p were determined using dual‑luciferase reporter assays. The results revealed that the SNHG7‑003 expression levels were downregulated in VSMCs exposed to ox‑LDL, while the overexpression (OE) of SNHG7‑003 significantly inhibited the proliferation, migration and invasion of VSMCs induced by ox‑LDL. Transfection with miR‑1306‑5p mimic abrogated the effects of the inhibitory effects induced by SNHG7‑003 OE. SIRT7 was validated to be a target gene of miR‑1306‑5p, exhibiting similar inhibitory effects as SNHG7‑003 in AS. It was also discovered to be involved in the regulatory effects of the SNHG7‑003/miR‑1306‑5p axis in VSMCs. On the whole, the findings of the present study indicate that SNHG7‑003 may inhibit the proliferation, migration and invasion of VSMCs via the miR‑1306‑5p/SIRT7 signaling pathway. These findings may provide a novel basis for the development of treatment strategies for AS.
长链非编码 RNA（lncRNA）已被发现参与多种类型疾病的进展，可能是动脉粥样硬化（AS）的有前途的生物标志物。本研究旨在探讨 lncRNA，小核仁 RNA 宿主基因 7-003（SNHG7-003）对血管平滑肌细胞（VSMC）增殖、迁移和侵袭的调控机制。首先用氧化低密度脂蛋白（ox-LDL）刺激 VSMC 以在高脂环境中模拟 AS。通过逆转录定量 PCR 分析 SNHG7-003、微小 RNA（miRNA/miR）-1306-5p 和 SIRT7 的表达水平，并通过细胞计数试剂盒-8、划痕愈合和 Transwell 测定分别确定这些因素对 VSMC 增殖、迁移和侵袭的影响。Western blot 分析也用于分析α-平滑肌肌动蛋白（α-SMA）、基质金属蛋白酶（MMP）2 和 MMP9 的蛋白表达水平。通过双荧光素酶报告基因测定确定 SNHG7-003 或 SIRT7 与 miR-1306-5p 之间的相互作用。结果显示，暴露于 ox-LDL 的 VSMC 中 SNHG7-003 的表达水平下调，而过表达（OE）SNHG7-003 显著抑制 ox-LDL 诱导的 VSMC 增殖、迁移和侵袭。转染 miR-1306-5p 模拟物可消除 SNHG7-003 OE 诱导的抑制作用。SIRT7 被验证为 miR-1306-5p 的靶基因，在 AS 中表现出与 SNHG7-003 相似的抑制作用。还发现它参与了 SNHG7-003/miR-1306-5p 轴在 VSMC 中的调节作用。总的来说，本研究的结果表明，SNHG7-003 可能通过 miR-1306-5p/SIRT7 信号通路抑制 VSMC 的增殖、迁移和侵袭。这些发现可能为 AS 治疗策略的发展提供新的依据。
