HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells
HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells
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DOI：
10.1080/14728222.2016.1220543
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发表时间：
2016-10-01
影响因子：
5.8
通讯作者：
Fusco, Alfredo
中科院分区：
文献类型：
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作者：
Colamaio, Marianna;Tosti, Nadia;Fusco, Alfredo
目的：多形性胶质母细胞瘤（GBM）由干细胞样细胞的小亚群发展而来，其被赋予自我更新、增殖和产生多种神经上皮谱系的后代的能力。这些细胞对常规化疗和放疗具有抗性，因此也是肿瘤复发的原因。HMGA1过表达已被证明与GBM的增殖、侵袭和血管生成相关，并影响结肠癌中癌症干细胞的自我更新。HMGA1在GBM肿瘤干细胞中的作用尚未完全了解。研究设计和方法：我们通过shRNA介导的HMGA1沉默研究了HMGA1在脑肿瘤干细胞（BTSC）自我更新、干性和对替莫唑胺的抗性中的作用。然后，我们表明HMGA1敲低降低了自我更新，球体形成效率和干性，并使BTSC对替莫唑胺敏感。有趣的是，HMGA1沉默也会导致降低肿瘤的启动能力在vivo.Conclusions：这些结果表明，HMGA1在癌症干细胞胶质瘤的发生和认可HMGA1作为一个合适的目标CSC特异性GBM治疗的关键作用。
Objective: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence.HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood.Research design and methods: We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing.Results: We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo.Conclusions: These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.