Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110122, People's Republic of China; Key Laboratory of Cell Biology, Ministry of Public Health of China, Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang 110122, People's Republic of China.
Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang 110004, People's Republic of China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, People's Republic of China.
Biochim Biophys Acta Mol Basis Dis. 2018 May;1864(5 Pt A):1783-1794. doi: 10.1016/j.bbadis.2018.02.022. Epub 2018 Mar 1.
The long non-coding RNA (lncRNA) PVT1 is reported to be involved in tumorigenesis and the progression of many malignancies. However, the function of PVT1 in gliomas remains unclarified. The present study demonstrated the expression level of PVT1 using qRT-PCR. The role of PVT1 in the regulation of biological behaviors of glioma cells was investigated using CCK-8 assay, Transwell assay and flow cytometry. The possible molecular mechanisms were also elucidated. In our results, PVT1 was up-regulated in glioma specimens and cell lines. Knockdown of PVT1 impaired the malignant behaviors of glioma cells via the suppression of proliferation, migration and invasion, as well as through promotion of apoptosis. Furthermore, PVT1 was identified to affect the glioma cells via binding to miR-190a-5p and miR-488-3p, which were down-regulated and played tumor suppressor roles in glioma cells. Up-regulated miR-190a-5p or miR-488-3p partially rescued the suppressive effect induced by PVT1 knockdown. Myocyte enhancer factor 2C (MEF2C) was a direct downstream target of miR-190a-5p and miR-488-3p, which was proved to be an oncogene and involved in the PVT1 knockdown induced regulation of biological behaviors of glioma cells. Over-expression of MEF2C up-regulated JAGGED1 by increasing the promoter activity of JAGGED1. PVT1 knockdown combined with miR-190a-5p and miR-488-3p over-expression contributed to the smallest tumor volume and the longest survivals in nude mice. In conclusion, PVT1-miR-190a-5p/miR-488-3p-MEF2C-JAGGED1 axis is involved in proliferation and progression of glioma. Thus, PVT1 may become a novel target in glioma therapy.
长链非编码 RNA（lncRNA）PVT1 被报道参与许多恶性肿瘤的发生和进展。然而，PVT1 在神经胶质瘤中的功能尚不清楚。本研究通过 qRT-PCR 检测 PVT1 的表达水平。通过 CCK-8 检测、Transwell 检测和流式细胞术研究 PVT1 对神经胶质瘤细胞生物学行为的调节作用。还阐明了可能的分子机制。在我们的结果中，PVT1 在神经胶质瘤标本和细胞系中上调。PVT1 的敲低通过抑制增殖、迁移和侵袭以及促进细胞凋亡来削弱神经胶质瘤细胞的恶性行为。此外，PVT1 通过与 miR-190a-5p 和 miR-488-3p 结合来影响神经胶质瘤细胞，miR-190a-5p 和 miR-488-3p 在神经胶质瘤细胞中下调并发挥肿瘤抑制作用。上调的 miR-190a-5p 或 miR-488-3p 部分挽救了 PVT1 敲低引起的抑制作用。肌细胞增强因子 2C（MEF2C）是 miR-190a-5p 和 miR-488-3p 的直接下游靶标，被证明是一种癌基因，参与 PVT1 敲低诱导的神经胶质瘤细胞生物学行为的调节。MEF2C 的过表达通过增加 JAGGED1 的启动子活性而上调 JAGGED1。PVT1 敲低与 miR-190a-5p 和 miR-488-3p 的过表达相结合，导致裸鼠的肿瘤体积最小和存活时间最长。总之，PVT1-miR-190a-5p/miR-488-3p-MEF2C-JAGGED1 轴参与神经胶质瘤的增殖和进展。因此，PVT1 可能成为神经胶质瘤治疗的新靶点。
