The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity.
The chromatin-modifying protein HMGA2 promotes atypical teratoid/rhabdoid cell tumorigenicity.
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DOI：
10.1097/nen.0000000000000161
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发表时间：
2015-02
影响因子：
3.2
通讯作者：
Raabe EH
中科院分区：
文献类型：
--
作者：
Kaur H;Hütt-Cabezas M;Weingart MF;Xu J;Kuwahara Y;Erdreich-Epstein A;Weissman BE;Eberhart CG;Raabe EH
非典型畸胎瘤/横纹肌样瘤（AT/RT）是一种侵袭性儿童中枢神经系统肿瘤。 AT/RT 的不良预后需要确定新的治疗靶点和策略。高迁移率基团 A2 (HMGA2) 是一种对发育至关重要的染色质修饰蛋白，可积极调节其他癌症类型的肿瘤生长、自我更新和侵袭。最近发现 HMGA2 在 AT/RT 组织中表达上调，但 HMGA2 在脑肿瘤中的作用仍不清楚。我们使用慢病毒短发夹RNA抑制AT/RT细胞系中的HMGA2，发现HMGA2的缺失导致细胞生长、增殖、集落形成减少和细胞凋亡增加。我们还发现，抑制 HMGA2 对体内原位异种移植肿瘤的生长产生负面影响，使小鼠的中位生存期从 58 天延长至 153 天，增加了一倍多。我们的结果表明 HMGA2 在体外和体内 AT/RT 中的作用，并证明 HMGA2 是这些致命儿科肿瘤的潜在治疗靶点。
Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive pediatric central nervous system tumor. The poor prognosis of AT/RT warrants identification of novel therapeutic targets and strategies. High mobility group A2 (HMGA2) is a developmentally important chromatin modifying protein that positively regulates tumor growth, self-renewal and invasion in other cancer types. HMGA2 was recently identified as being upregulated in AT/RT tissue, but the role of HMGA2 in brain tumors remains unknown. We used lentiviral short hairpin RNA to suppress HMGA2 in AT/RT cell lines and found that loss of HMGA2 led to decreased cell growth, proliferation, colony formation and increased apoptosis. We also found that suppression of HMGA2 negatively affected in vivo orthotopic xenograft tumor growth, more than doubling median survival of the mice from 58 days to 153 days. Our results indicate a role for HMGA2 in AT/RT in vitro and in vivo and demonstrate that HMGA2 is a potential therapeutic target in these lethal pediatric tumors.