Chen Hua, Liu Liang, Li Xiaojian, Shi Yan, Liu Ning
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029, Jiangsu, China.
Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical UniversityNanjing 210006, Jiangsu, China.
Am J Cancer Res. 2018 Feb 1;8(2):291-301. eCollection 2018.
MicroRNA-1294 (miR-1294) has been reported to be involved in the progression of esophageal squamous cell carcinoma. However, the function and the mechanisms of miR-1294 in glioma remain unclear. In this study, we explore the potential biological roles of miR-1294 in glioma cell lines. First, we detected the aberrant down-regulation of miR-1294 in glioma tissues and cell lines. Second, we determined that miR-1294 suppresses the proliferation, migration and invasiveness and enhances the chemosensitivity of glioma cells lines to temozolomide. Third, we found that the targeting protein for Xenopus kinesin-like protein 2 (TPX2) is the functional target of miR-1294; miR-1294 acts through TPX2 to exert an important biological effect in glioma. Importantly, TPX2 knockdown had the same effect on glioma cell lines as miR-1294 overexpression. In addition, when TPX2 was up-regulated in these cells, the effects of miR-1294 on glioma cell lines were suppressed. Moreover, the effect of miR-1294 on glioma was verified using a xenograft model. These findings demonstrated that miR-1294 inhibits the development of glioma by targeting TPX2. These findings provide a new potential therapeutic target for glioma treatment.
据报道，微小RNA - 1294（miR - 1294）参与食管鳞状细胞癌的进展。然而，miR - 1294在胶质瘤中的功能和机制仍不清楚。在本研究中，我们探讨了miR - 1294在胶质瘤细胞系中的潜在生物学作用。首先，我们检测到miR - 1294在胶质瘤组织和细胞系中异常下调。其次，我们确定miR - 1294抑制胶质瘤细胞系的增殖、迁移和侵袭，并增强其对替莫唑胺的化学敏感性。第三，我们发现非洲爪蟾驱动蛋白样蛋白2（TPX2）的靶向蛋白是miR - 1294的功能靶点；miR - 1294通过TPX2发挥作用，在胶质瘤中发挥重要的生物学效应。重要的是，敲低TPX2对胶质瘤细胞系的作用与过表达miR - 1294相同。此外，当这些细胞中TPX2上调时，miR - 1294对胶质瘤细胞系的作用受到抑制。此外，使用异种移植模型验证了miR - 1294对胶质瘤的作用。这些发现表明，miR - 1294通过靶向TPX2抑制胶质瘤的发展。这些发现为胶质瘤治疗提供了一个新的潜在治疗靶点。
