Department of Cardiology, The Second Affiliated Hospital of Xi'an Medical University, Center for Clinical Medical Research of Cardiovascular Diseases in Shaanxi Province, Xi'an, Shaanxi 710038, P.R. China.
Electrocardiographic Room, Ankang Central Hospital, Ankang, Shaanxi 725000, P.R. China.
Int J Mol Med. 2019 Dec;44(6):1991-2002. doi: 10.3892/ijmm.2019.4357. Epub 2019 Sep 27.
Diabetic patients with high glucose exhibit vascular smooth muscle cell (VSMC) alteration. Thrombotic disease is related to erosion of an unstable plaque, the instability of which leads to ruptures, for example, a thin fibrous cap derived from VSMCs. VSMC proliferation, migration and invasion are related to thrombotic diseases, including atherosclerosis. MicroRNA‑19a (miR‑19a) has been reported to have pleiotropic functions in cancer cell survival, apoptosis and migration. The present study aimed to investigate the effect of miR‑19a on VSMC proliferation, migration and invasion, and its mechanism. Cell Counting Kit‑8 and a propidium iodide kit were used to determine the proliferation and cycle of VSMCs. A cell migration assay was performed by scratching and Matrigel was used in a cell invasion assay. miR‑19a binding to Ras homolog family member B (RHOB), and their protein and mRNA expressions were determined by performing a dual luciferase assay, western blotting and reverse transcription‑quantitative PCR, respectively. It was demonstrated that miR‑19a promoted the proliferation, migration and invasion of VSMCs, promoted the expressions of dual specificity phosphatase Cdc25A (CDC25A), cyclinD1, matrix metalloproteinase (MMP)‑2, MMP‑9, α‑smooth muscle actin (α‑SMA) and smooth muscle 22α (SM22α), and inhibited suppressor of cytokine signaling 3 and RHOB expressions in VSMCs, while miR‑19a had no effect on the expression of T‑cell intracellular antigen‑1. The miR‑19a site bound to the RHOB gene position and inhibited RHOB to promote VSMC proliferation, invasion and migration, and increased MMP‑2, MMP‑9, α‑SMA and SM22α expressions. The present study suggested that miR‑19a could promote VSMC proliferation, migration and invasion via the cyclinD1/CDC25A and MMP/α‑SMA/SM22α signaling pathways. Moreover, miR‑19a promoted proliferation, migration and invasion via the MMP/α‑SMA/SM22α signaling pathway by inhibiting RHOB, suggesting that miR‑19a is a possible regulatory factor of RHOB.
患有高血糖的糖尿病患者表现出血管平滑肌细胞 (VSMC) 改变。血栓性疾病与不稳定斑块的侵蚀有关，不稳定斑块会导致破裂，例如，源自 VSMC 的薄纤维帽。VSMC 的增殖、迁移和侵袭与包括动脉粥样硬化在内的血栓性疾病有关。微小 RNA-19a (miR-19a) 已被报道在癌细胞存活、凋亡和迁移中具有多效性功能。本研究旨在探讨 miR-19a 对 VSMC 增殖、迁移和侵袭的影响及其机制。使用细胞计数试剂盒-8 和碘化丙啶试剂盒测定 VSMC 的增殖和细胞周期。通过划痕实验进行细胞迁移测定，并使用 Matrigel 进行细胞侵袭测定。通过双荧光素酶测定、western blot 分析和逆转录-定量 PCR 分别测定 miR-19a 与 Ras 同源家族成员 B (RHOB) 的结合及其蛋白和 mRNA 表达。结果表明，miR-19a 促进了 VSMC 的增殖、迁移和侵袭，促进了双特异性磷酸酶 Cdc25A (CDC25A)、细胞周期蛋白 D1、基质金属蛋白酶 (MMP)-2、MMP-9、α-平滑肌肌动蛋白 (α-SMA) 和平滑肌 22α (SM22α) 的表达，并抑制了 VSMC 中细胞因子信号转导抑制因子 3 和 RHOB 的表达，而 miR-19a 对 T 细胞内抗原-1 的表达没有影响。miR-19a 与 RHOB 基因位置结合并抑制 RHOB 以促进 VSMC 增殖、侵袭和迁移，并增加 MMP-2、MMP-9、α-SMA 和 SM22α 的表达。本研究表明，miR-19a 可通过 cyclinD1/CDC25A 和 MMP/α-SMA/SM22α 信号通路促进 VSMC 的增殖、迁移和侵袭。此外，miR-19a 通过抑制 RHOB 促进增殖、迁移和侵袭，通过 MMP/α-SMA/SM22α 信号通路，提示 miR-19a 可能是 RHOB 的一个调节因子。
