The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma.
The transcriptional modulator HMGA2 promotes stemness and tumorigenicity in glioblastoma.
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DOI：
10.1016/j.canlet.2016.04.020
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发表时间：
2016-07-10
期刊：
影响因子：
9.7
通讯作者：
Raabe, Eric H.
中科院分区：
文献类型：
--
作者：
Kaur, Harpreet;Ali, Sabeen Zulfiqar;Huey, Lauren;Hutt-Cabezas, Marianne;Taylor, Isabella;Mao, Xing-gang;Weingart, Melanie;Chu, Qian;Rodriguez, Fausto J.;Eberhart, Charles G.;Raabe, Eric H.
胶质母细胞瘤（GBM）含有一群干细胞样细胞，可促进肿瘤侵袭和对治疗的抵抗。识别和靶向GBM中的干细胞因子可能会导致更有效的治疗方法的发展。高迁移率族AT-钩2（HMGA 2）是一种转录调节因子，介导正常和癌症干细胞的运动性和自我更新。与正常脑相比，我们在大多数原发性人GBM肿瘤和细胞系中鉴定出HMGA 2表达增加。此外，与CD 133-细胞相比，CD 133 + GBM神经球细胞中HMGA 2表达增加。用慢病毒短发夹RNA（shRNA）靶向HMGA 2导致GBM干性、侵袭性和致瘤性降低。HMGA 2在GBM细胞系中的异位表达促进了干细胞性、侵袭性和致瘤性。我们的数据表明，靶向GBM中的HMGA 2可能是治疗有益的。
Glioblastoma (GBM) contains a population of stem-like cells that promote tumor invasion and resistance to therapy. Identifying and targeting stem cell factors in GBM may lead to the development of more effective therapies. High Mobility Group AT-hook 2 (HMGA2) is a transcriptional modulator that mediates motility and self-renewal in normal and cancer stem cells. We identified increased expression of HMGA2 in the majority of primary human GBM tumors and cell lines compared to normal brain. Additionally, HMGA2 expression was increased in CD133+ GBM neurosphere cells compared to CD133- cells. Targeting HMGA2 with lentiviral short hairpin RNA (shRNA) led to decreased GBM stemness, invasion, and tumorigenicity. Ectopic expression of HMGA2 in GBM cell lines promoted stemness, invasion, and tumorigenicity. Our data suggests that targeting HMGA2 in GBM may be therapeutically beneficial.
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