Gui Fu, Hong Zhengdong, You Zhipeng, Wu Hongxi, Zhang Yulan
Department of Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China.
Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China.
Cell Biol Int. 2016 Dec;40(12):1294-1302. doi: 10.1002/cbin.10678. Epub 2016 Sep 27.
MicroRNA-21 (miR-21) was reported to act as an oncogene during the development of many human tumors. However, little was revealed about the function of miR-21 in retinoblastoma (RB). In this study, we examined the expression of miR-21 in RB tissues and explored the relationship between miR-21 and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-OH kinase (PI3K)/AKT signal. Quantitative real-time PCR (qRT-PCR) results showed that the level of miR-21 in RB tissues was higher than that in retinal normal tissues. In Weri-Rb-1 cells, miR-21 inhibitor suppressed the expression of miR-21 and cell viability, but improved cell apoptotic rates by modulating the levels of PDCD4, Bax, and Bcl-2. Meanwhile, miR-21 inhibitor suppressed cell migration and invasion via inhibiting the protein levels of MMP2 and MMP9 and significantly affected the expression of PTEN, PI3K, and p-AKT. Taken together, miR-21 inhibitor suppressed cell proliferation, migration, and invasion via the PTEN/PI3K/AKT signal. These findings revealed the molecular basis of miR-21 functioning in the progression of RB and provided a new means for cell therapy in RB.
据报道，微小RNA-21（miR-21）在许多人类肿瘤的发生发展过程中发挥癌基因的作用。然而，关于miR-21在视网膜母细胞瘤（RB）中的功能却鲜有报道。在本研究中，我们检测了miR-21在RB组织中的表达，并探讨了miR-21与磷酸酶和张力蛋白同源物（PTEN）/磷脂酰肌醇-3-羟基激酶（PI3K）/AKT信号之间的关系。定量实时聚合酶链反应（qRT-PCR）结果显示，RB组织中miR-21的水平高于视网膜正常组织。在Weri-Rb-1细胞中，miR-21抑制剂抑制了miR-21的表达和细胞活力，但通过调节PDCD4、Bax和Bcl-2的水平提高了细胞凋亡率。同时，miR-21抑制剂通过抑制MMP2和MMP9的蛋白水平抑制细胞迁移和侵袭，并显著影响PTEN、PI3K和p-AKT的表达。综上所述，miR-21抑制剂通过PTEN/PI3K/AKT信号抑制细胞增殖、迁移和侵袭。这些发现揭示了miR-21在RB进展中发挥作用的分子基础，并为RB的细胞治疗提供了新的手段。
