National Hepatobiliary and Enteric Surgery Research Center, Central South University, Changsha 410008, P.R. China.
Int J Mol Med. 2013 Jul;32(1):101-7. doi: 10.3892/ijmm.2013.1365. Epub 2013 Apr 29.
microRNA-124 (miR-124) plays an important role in regulating growth, invasiveness, stem-like traits, differentiation and apoptosis of glioblastoma cells. PPP1R3L, an inhibitory member of the apoptosis-stimulating protein of p53 family (IASPP), is also able to affect growth, cell cycle progression, metastasis and apoptosis of various types of cancer. To investigate the regulation of PPP1R13L expression by miR-124 and their effects on proliferation, cell cycle transition and invasion in glioblastoma cells, U251 and U373 glioblastoma cells were transfected with miR-124 mimics, its negative control (NC) or an inhibitor. We found that miR-124 was downregulated in glioblastoma tissues, and inversely regulated PPP1R13L expression in U251 and U373 glioblastoma cells. PPP1R13L was found to be a direct target of miR-124 in glioblastoma cells. Overexpression of miR-124 inhibited proliferation, G1/S transition and invasiveness in glioblastoma cells. miR-124 downregulation-mediated malignant progression of glioblastoma was partly attributed to increased PPP1R13L expression. Consequently, our findings provide a molecular basis for the role of miR-124/PPP1R13L in the progression of human glioblastoma and suggest a novel target for the treatment of glioblastoma.
miR-124（miR-124）在调节神经胶质瘤细胞的生长、侵袭、干细胞样特征、分化和凋亡中发挥重要作用。凋亡刺激蛋白 p53 家族抑制成员 PPP1R3L（IASPP）也能够影响各种类型癌症的生长、细胞周期进程、转移和凋亡。为了研究 miR-124 对 PPP1R13L 表达的调节及其对神经胶质瘤细胞增殖、细胞周期转换和侵袭的影响，用 miR-124 模拟物、其阴性对照（NC）或抑制剂转染 U251 和 U373 神经胶质瘤细胞。我们发现 miR-124 在神经胶质瘤组织中下调，并在 U251 和 U373 神经胶质瘤细胞中反向调节 PPP1R13L 的表达。PPP1R13L 是神经胶质瘤细胞中 miR-124 的直接靶标。miR-124 的过表达抑制神经胶质瘤细胞的增殖、G1/S 转换和侵袭。miR-124 下调介导的神经胶质瘤恶性进展部分归因于 PPP1R13L 表达的增加。因此，我们的研究结果为 miR-124/PPP1R13L 在人类神经胶质瘤进展中的作用提供了分子基础，并为神经胶质瘤的治疗提供了新的靶点。
