Lin Qiang, Mao Yurong, Song Yunlin, Huang Dongfeng
Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
Intensive Care Unit, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Autonomous Region 830011, P.R. China.
Mol Med Rep. 2015 Oct;12(4):5709-14. doi: 10.3892/mmr.2015.4185. Epub 2015 Aug 5.
MicroRNA‑34a (miR‑34a) is a direct target of p53 and was reported to induce cell cycle arrest, apoptosis and senescence. Inhibition of the NAD‑dependent deacetylase sirtuin‑1 (SIRT1) by miR‑34a leads to an increase in acetylated p53, which promotes cell apoptosis. B‑cell lymphoma 2 (Bcl‑2) is also involved in apoptosis, and was originally characterized with respect to its role in controlling outer mitochondrial membrane integrity. The effect of miR‑34a in PC12 cells has not yet been reported. In the present study, it was hypothesized that Bcl‑2 and SIRT1 may be critical downstream targets of miR‑34a that participate in apoptosis induction. miR‑34a mimics and inhibitors were transfected into PC12 cells, and the apoptosis and proliferation rates were compared between groups. It was demonstrated that induction of miR‑34a promotes apoptosis and senescence, inhibits proliferation, and leads to marked alterations in SIRT1, Bcl‑12 and acetyl (ac)‑p53 expression. These data indicate that miR‑34a may be important in neuropathy.
微小RNA-34a(miR-34a)是p53的直接靶点,据报道可诱导细胞周期停滞、凋亡和衰老。miR-34a对烟酰胺腺嘌呤二核苷酸(NAD)依赖性脱乙酰酶沉默调节蛋白1(SIRT1)的抑制作用会导致乙酰化p53增加,从而促进细胞凋亡。B细胞淋巴瘤2(Bcl-2)也参与凋亡,最初是根据其在控制线粒体外膜完整性方面的作用来表征的。miR-34a在PC12细胞中的作用尚未见报道。在本研究中,推测Bcl-2和SIRT1可能是参与凋亡诱导的miR-34a的关键下游靶点。将miR-34a模拟物和抑制剂转染到PC12细胞中,并比较各组之间的凋亡率和增殖率。结果表明,miR-34a的诱导促进凋亡和衰老,抑制增殖,并导致SIRT1、Bcl-12和乙酰化(ac)-p53表达发生明显改变。这些数据表明,miR-34a在神经病变中可能很重要。