RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma
RNA-Binding Protein Musashi1 Is a Central Regulator of Adhesion Pathways in Glioblastoma
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DOI：
10.1128/mcb.00410-15
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发表时间：
2015-09-01
影响因子：
5.3
通讯作者：
Penalva, Luiz O. F.
中科院分区：
文献类型：
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作者：
Uren, Philip J.;Vo, Dat T.;Penalva, Luiz O. F.
保守的RNA结合蛋白Musashi1（MSI1）已成为许多实体瘤（包括胶质母细胞瘤）的关键致癌因子。然而，其作用机制尚未全面建立。为了全面识别其靶基因并确定其影响胶质母细胞瘤表型的主要途径，我们进行了单个核苷酸分辨率交联和免疫沉淀（iCLIP）实验。我们证实了MSI1对特定结构背景下的UAG序列具有偏好性，特别是在3'非翻译区。尽管在内含子序列中也发现了许多结合位点，但我们的RNA转录组测序分析并不支持MSI1是胶质母细胞瘤细胞中剪接的主要调节因子的观点。MSI1靶mRNA编码在细胞增殖和细胞粘附的多种途径中起作用的蛋白质。由于这些协会表明MSI1潜在的新作用，我们研究了其对胶质母细胞瘤细胞粘附，形态，迁移和侵袭的影响。已知这些过程支持胶质母细胞瘤的扩散和复发，与转移是复发和进展的主要驱动力的其他肿瘤相反。
The conserved RNA-binding protein Musashi1 (MSI1) has emerged as a key oncogenic factor in numerous solid tumors, including glioblastoma. However, its mechanism of action has not yet been established comprehensively. To identify its target genes comprehensively and determine the main routes by which it influences glioblastoma phenotypes, we conducted individual-nucleotide resolution cross-linking and immunoprecipitation (iCLIP) experiments. We confirmed that MSI1 has a preference for UAG sequences contained in a particular structural context, especially in 3' untranslated regions. Although numerous binding sites were also identified in intronic sequences, our RNA transcriptome sequencing analysis does not favor the idea that MSI1 is a major regulator of splicing in glioblastoma cells. MSI1 target mRNAs encode proteins that function in multiple pathways of cell proliferation and cell adhesion. Since these associations indicate potentially new roles for MSI1, we investigated its impact on glioblastoma cell adhesion, morphology, migration, and invasion. These processes are known to underpin the spread and relapse of glioblastoma, in contrast to other tumors where metastasis is the main driver of recurrence and progression.