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miR-1261/circ-PTPRZ1/PAK1 通路调控神经胶质瘤细胞的生长和侵袭。

MiR-1261/circ-PTPRZ1/PAK1 pathway regulates glioma cell growth and invasion.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511447, Guangdong, China.

Department of Anesthesiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 511447, Guangdong, China.

出版信息

Hum Cell. 2019 Oct;32(4):540-547. doi: 10.1007/s13577-019-00271-3. Epub 2019 Jul 30.

Abstract

Glioma is the most common primary brain tumor in adults, with high malignancy and poor prognosis. According to the research in these years, the relationship between circular RNAs (circRNAs) and glioma development is abnormally close. Studies on circRNAs in glioma cells revealed that miR-1261 had almost completely matched binding site on the circ-PTPRZ1 sequence, and dual-luciferase reporter gene assay confirmed that circ-PTPRZ1 was a target gene of miR-1261. MiR-1261 inhibited circ-PTPRZ1 expression in glioma cells, while circ-PTPRZ1 did not affect miR-1261 expression. At the same time, circ-PTPRZ1 could promote p-PAK1 expression, while miR-1261 suppressed the activation of PAK1 by regulating the expression of circ-PTPRZ1. Biological behaviors of glioma cells were detected, circ-PTPRZ1 enhanced cell proliferation and invasion, and inhibited cell apoptosis; miR-1261 had the opposite effects, and could terminate the above effects of circ-PTPRZ1. When co-transfected with PAK1 siRNAs and circ-PTPRZ1 over-expression vector, the changes of above biological behaviors were not obvious. Therefore, in glioma cells, the expression of circ-PTPRZ1/PAK1 is regulated by miR-1261, which affects the proliferation, apoptosis, and invasion. This finding provides another powerful evidence for the role of circRNAs in glioma.

摘要

神经胶质瘤是成人中最常见的原发性脑肿瘤,具有高度恶性和预后不良的特点。根据近年来的研究,环状 RNA(circRNA)与神经胶质瘤的发生发展关系异常密切。对神经胶质瘤细胞中 circRNAs 的研究表明,miR-1261 在 circ-PTPRZ1 序列上几乎完全匹配结合位点,双荧光素酶报告基因实验证实 circ-PTPRZ1 是 miR-1261 的靶基因。miR-1261 抑制神经胶质瘤细胞中 circ-PTPRZ1 的表达,而 circ-PTPRZ1 不影响 miR-1261 的表达。同时,circ-PTPRZ1 可以促进 p-PAK1 的表达,而 miR-1261 通过调节 circ-PTPRZ1 的表达抑制 PAK1 的激活。检测神经胶质瘤细胞的生物学行为,circ-PTPRZ1 增强细胞增殖和侵袭,抑制细胞凋亡;miR-1261 则具有相反的作用,并能终止 circ-PTPRZ1 的上述作用。当共转染 PAK1 siRNAs 和 circ-PTPRZ1 过表达载体时,上述生物学行为的变化并不明显。因此,在神经胶质瘤细胞中,circ-PTPRZ1/PAK1 的表达受 miR-1261 调控,影响增殖、凋亡和侵袭。这一发现为 circRNAs 在神经胶质瘤中的作用提供了另一个有力证据。

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