RNAi-mediated inhibition of MSP58 decreases tumour growth, migration and invasion in a human glioma cell line.
RNAi-mediated inhibition of MSP58 decreases tumour growth, migration and invasion in a human glioma cell line.
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RNAi 介导的 MSP58 抑制可降低人神经胶质瘤细胞系中的肿瘤生长、迁移和侵袭
DOI：
10.1111/j.1582-4934.2008.00499.x
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发表时间：
2009-11
影响因子：
5.3
通讯作者：
Yao L
中科院分区：
文献类型：
--
作者：
Lin W;Zhang J;Zhang J;Liu X;Fei Z;Li X;Davidovic L;Tang Z;Shen L;Deng Y;Yang A;Han H;Zhang X;Yao L
MSP 58是一种分子量为58 kD的核微球蛋白，是一种进化上保守的核蛋白，参与基因转录调控和恶性转化。通过实时PCR对mRNA表达的分析显示，MSP 58在29%的高级别胶质母细胞瘤组织以及四种胶质母细胞瘤细胞系中显著上调。在本研究中，我们进一步评估MSP58在U251胶质瘤细胞增殖，迁移，侵袭和肿瘤生长在体内的生物学功能，通过特异性MSP58敲低使用短发夹RNA（shRNA）。我们发现，MSP58耗竭抑制神经胶质瘤细胞的生长，主要是通过诱导细胞周期停滞，而不是凋亡。MSP58缺失也降低了胶质瘤细胞的侵袭能力和软琼脂中的非贴壁依赖性集落形成。此外，抑制MSP58表达显著损害了裸鼠中胶质瘤异种移植物的生长。最后，细胞周期相关基因阵列揭示了潜在的分子机制，有助于在MSP 58耗尽胶质瘤细胞的细胞周期停滞。总之，我们的数据突出了MSP58在胶质瘤进展中的重要性，并为MSP58作为胶质瘤治疗的新候选靶点提供了生物学基础。
MSP58, a 58-kD nuclear microspherule protein, is an evolutionarily conserved nuclear protein implicated in the regulation of gene transcription as well as in malignant transformation. An analysis of mRNA expression by real-time PCR revealed that MSP58 was significantly up-regulated in 29% of high-grade glioblastoma tissues as well as in four glioblastoma cell lines. In the present study, we further evaluated the biological functions of MSP58 in U251 glioma cell proliferation, migration, invasion and tumour growth in vivo by specific MSP58 knockdown using short hairpin RNA (shRNA). We found that MSP58 depletion inhibited glioma cell growth, primarily by inducing cell cycle arrest rather than apoptosis. MSP58 depletion also decreased the invasive capability of glioma cells and anchorage-independent colony formation in soft agar. Moreover, suppression of MSP58 expression significantly impaired the growth of glioma xenografts in nude mice. Finally, a cell cycle-associated gene array revealed potential molecular mechanisms contributing to cell cycle arrest in MSP58-depleted glioma cells. In summary, our data highlight the importance of MSP58 in glioma progression and provided a biological basis for MSP58 as a novel candidate target for treatment of glioma.