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MicroRNA-30b-5p 通过靶向富含脯氨酸的跨膜蛋白 2 在胶质母细胞瘤中的致癌作用。

Oncogenic Role of MicroRNA-30b-5p in Glioblastoma Through Targeting Proline-Rich Transmembrane Protein 2.

机构信息

Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, P.R. China.

Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.

出版信息

Oncol Res. 2018 Mar 5;26(2):219-230. doi: 10.3727/096504017X14944585873659. Epub 2017 May 17.

Abstract

MicroRNAs (miRs) have been found to play promoting or suppressive roles in different human cancers. However, the exact regulatory mechanism of miR-30b in glioblastoma remains unknown. Here we have shown that the expression of miR-30b is significantly increased in glioblastoma tissues and cell lines. Moreover, a high expression of miR-30b is significantly associated with a shorter survival time for glioblastoma patients. Knockdown of miR-30b caused a significant reduction in the proliferation, migration, and invasion of U87 and A172 cells. Proline-rich transmembrane protein 2 (PRRT2) was further identified as a novel target gene of miR-30b, and its protein expression is negatively regulated by miR-30b in U87 and A172 cells. Furthermore, PRRT2 is significantly downregulated in glioblastoma tissues and cell lines, and we found an inverse correlation between miR-30b and PRRT2 expression in glioblastoma tissues. In addition, inhibition of PRRT2 reversed the suppressive effect of miR-30b downregulation on the malignant phenotypes of U87 and A172 cells. Accordingly, we demonstrated that miR-30b promotes glioblastoma cell proliferation, migration, and invasion via targeting PRRT2. Therefore, miR-30b may be used as a promising therapeutic target for glioblastoma.

摘要

微小 RNA(miRs)已被发现于多种人类癌症中发挥促进或抑制作用。然而,miR-30b 在胶质母细胞瘤中的确切调控机制仍不清楚。本研究显示 miR-30b 在胶质母细胞瘤组织和细胞系中表达显著上调。此外,miR-30b 高表达与胶质母细胞瘤患者生存时间较短显著相关。miR-30b 敲低可显著降低 U87 和 A172 细胞的增殖、迁移和侵袭能力。脯氨酸丰富跨膜蛋白 2(PRRT2)进一步被鉴定为 miR-30b 的一个新的靶基因,其蛋白表达在 U87 和 A172 细胞中受 miR-30b 负调控。此外,PRRT2 在胶质母细胞瘤组织和细胞系中表达显著下调,我们在胶质母细胞瘤组织中发现 miR-30b 与 PRRT2 表达呈负相关。此外,抑制 PRRT2 可逆转 miR-30b 下调对 U87 和 A172 细胞恶性表型的抑制作用。因此,我们证实 miR-30b 通过靶向 PRRT2 促进胶质母细胞瘤细胞的增殖、迁移和侵袭。因此,miR-30b 可能作为胶质母细胞瘤有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a2da/7844647/87308fd2e3de/OR-26-219-g001.jpg

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