Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China.
Department of Neurosurgery, Second Affiliated Hospital of Xi'an Medical University, Xi'an, 710038, Shaanxi Province, China.
Biochimie. 2019 Jul;162:116-124. doi: 10.1016/j.biochi.2019.04.014. Epub 2019 Apr 14.
Cell cycle-related and expression elevated protein in tumor (CREPT) is emerging as a novel cancer-related gene that is dysregulated in many kinds of malignancies. However, the expression and biological role of CREPT in glioma remains unclear. In the present study, we aimed to explore the potential function and regulation mechanism of CREPT in glioma. Results showed that CRETP expression was significantly upregulated in glioma cell lines. Depletion of CREPT by siRNA-mediated gene silencing markedly decreased the proliferative and invasive capabilities of glioma cells. Bioinformatics analysis predicted CREPT as a target gene of microRNA-596 (miR-596), which was further verified by real-time quantitative polymerase chain reaction and Western blot analysis. miR-596 was significantly decreased in glioma tissues and cell lines, and inversely correlated with CREPT expression in clinical specimens. Knockdown of CREPT or overexpression of miR-596 significantly restricted the activation of Wnt/β-catenin signaling in glioma cells. Moreover, overexpression of CREPT partially reversed the miR-596-mediated inhibitory effect on proliferation, invasion and Wnt/β-catenin signaling in glioma cells. Overall, these results demonstrate that CREPT exerts an oncogenic role in glioma and its expression is regulated by miR-596. Our study highlights the important role miR-596/CREPT/Wnt/β-catenin signaling axis may play in glioma.
肿瘤细胞周期相关和表达上调蛋白（CREPT）作为一种新的癌相关基因，在许多恶性肿瘤中失调。然而，CREPT 在神经胶质瘤中的表达和生物学作用尚不清楚。在本研究中，我们旨在探讨 CREPT 在神经胶质瘤中的潜在功能和调控机制。结果表明，CRETP 在神经胶质瘤细胞系中表达明显上调。通过 siRNA 介导的基因沉默使 CREPT 耗竭，明显降低了神经胶质瘤细胞的增殖和侵袭能力。生物信息学分析预测 CREPT 是 microRNA-596（miR-596）的靶基因，通过实时定量聚合酶链反应和 Western blot 分析进一步验证。miR-596 在神经胶质瘤组织和细胞系中显著降低，与临床标本中 CREPT 的表达呈负相关。敲低 CREPT 或过表达 miR-596 可显著抑制神经胶质瘤细胞中 Wnt/β-catenin 信号通路的激活。此外，过表达 CREPT 部分逆转了 miR-596 对神经胶质瘤细胞增殖、侵袭和 Wnt/β-catenin 信号通路的抑制作用。综上所述，这些结果表明 CREPT 在神经胶质瘤中发挥致癌作用，其表达受 miR-596 调节。我们的研究强调了 miR-596/CREPT/Wnt/β-catenin 信号轴在神经胶质瘤中可能发挥的重要作用。
