RNA binding protein RBM14 promotes radio-resistance in glioblastoma by regulating DNA repair and cell differentiation.
RNA binding protein RBM14 promotes radio-resistance in glioblastoma by regulating DNA repair and cell differentiation.
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RNA结合蛋白RBM14通过调节DNA修复和细胞分化来促进胶质母细胞瘤的放射性。
DOI：
10.18632/oncotarget.1924
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发表时间：
2014-05-15
期刊：
影响因子：
--
通讯作者：
Kai M
中科院分区：
文献类型：
--
作者：
Yuan M;Eberhart CG;Kai M
多形性胶质母细胞瘤（GBM）是最具侵袭性和致命性的脑肿瘤类型。GBM患者的标准治疗是手术，然后是放疗和/或化疗，但肿瘤总是复发。传统疗法似乎失败了，因为它们只消除了大部分肿瘤，并保留了称为肿瘤起始细胞的干细胞样细胞群。GBM肿瘤起始细胞的干细胞样状态和DNA损伤反应的优先激活有助于其放射抗性和复发。这种有效激活损伤反应和维持干细胞样状态的分子机制仍然难以捉摸。在这里，我们表明RBM 14控制DNA修复途径，也阻止GBM球体中的细胞分化，导致辐射抗性。RBM 14的敲低影响GBM球体维持并在细胞水平上使抗辐射GBM细胞敏感。我们证明RBM 14敲低阻断了体内照射后GBM的再生长。此外，RBM 14通过控制DNA-PK依赖性非同源末端连接（NHEJ）途径刺激DNA修复。这些结果揭示了RNA结合蛋白RBM 14在控制肿瘤起始细胞的DNA修复和维持中的意想不到的功能。靶向RBM 14依赖性通路可以防止肿瘤复发并完全根除致命疾病。
Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Standard treatment for GBM patients is surgery followed by radiotherapy and/or chemotherapy, but tumors always recur. Traditional therapies seem to fail because they eliminate only the bulk of the tumors and spare a population of stem-like cells termed tumor-initiating cells. The stem-like state and preferential activation of DNA damage response in the GBM tumor-initiating cells contribute to their radio-resistance and recurrence. The molecular mechanisms underlying this efficient activation of damage response and maintenance of stem-like state remain elusive. Here we show that RBM14 controls DNA repair pathways and also prevents cell differentiation in GBM spheres, causing radio-resistance. Knockdown of RBM14 affects GBM sphere maintenance and sensitizes radio-resistant GBM cells at the cellular level. We demonstrate that RBM14 knockdown blocks GBM regrowth after irradiation in vivo. In addition, RBM14 stimulates DNA repair by controlling the DNA-PK-dependent non-homologous end-joining (NHEJ) pathway. These results reveal unexpected functions of the RNA-binding protein RBM14 in control of DNA repair and maintenance of tumor-initiating cells. Targeting the RBM14-dependent pathway may prevent recurrence of tumors and eradicate the deadly disease completely.
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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作者：
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DOI：
10.1073/pnas.0400726101
发表时间：
2004-05-18
影响因子：
11.1
作者：
Seluanov, A;Mittelman, D;Gorbunova, V
通讯作者：
Gorbunova, V