A Unique Spectrum of Spontaneous Tumors in Dino Knockout Mice Identifies Tissue-Specific Requirements for Tumor Suppression.
A Unique Spectrum of Spontaneous Tumors in Dino Knockout Mice Identifies Tissue-Specific Requirements for Tumor Suppression.
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Dino基因敲除小鼠中自发性肿瘤的独特光谱确定了组织特异性抑制的需求。
作者：
在这里，我们报告了Dino，一种P53信号转导所需的lncRNA，抑制了小鼠的自发肿瘤形成。与DINO+/+对照相比，DINO−/−小鼠患上的恶性肿瘤明显更多，主要包括肉瘤、B细胞淋巴瘤和其他罕见肿瘤。虽然Dino−/−小鼠的淋巴瘤和肉瘤的患病率与P53基因缺失的小鼠相似，但出现了重要的区别。P53基因缺失的小鼠主要发生T细胞淋巴瘤；然而，在Dino−/−小鼠中没有观察到自发性T细胞淋巴瘤。Dino−/−小鼠中的自发肿瘤不是p53缺失肿瘤谱的表型，而是类似于人类癌症的谱，在人类癌症中，Dino的甲基化反复被甲基化沉默，其方式与TP53改变互斥，这表明人类和小鼠的类似组织需要Dino来抑制肿瘤。与Dino在肿瘤抑制中的组织特异性作用一致，Dino的缺失对辐射诱导的T细胞淋巴瘤和癌基因驱动的髓母细胞瘤的发展没有影响，这些肿瘤因P53的丢失而加速。综上所述，这些数据表明，Dino是一种有效的肿瘤抑制分子，对小鼠和人类的特定组织亚集具有特异性。
Here, we report that Dino, a lncRNA required for p53 signaling, suppresses spontaneous tumorigenesis in mice. Dino−/− mice develop significantly more malignant tumors than Dino+/+ littermate controls, consisting predominantly of sarcomas, B cell lymphomas and additional rare tumors. While the prevalence of lymphomas and sarcomas in Dino−/− mice is similar to that of mice with p53 loss, important distinctions emerged. p53-null mice predominantly develop T cell lymphomas; however, no spontaneous T cell lymphoma was observed in Dino−/− mice. Rather than being a phenocopy of the p53-null tumor spectrum, spontaneous tumors in Dino−/− mice resemble the spectrum of human cancers in which DINO is recurrently silenced by methylation in a manner that is mutually exclusive with TP53 alterations, suggesting that similar tissues in human and mouse require DINO for tumor suppression. Consistent with a tissue-specific role for Dino in tumor suppression, loss of Dino had no impact on the development of radiation-induced T cell lymphoma and oncogene-driven medulloblastoma, tumors that are accelerated by the loss of p53. Taken together, these data indicate that Dino serves as a potent tumor suppressor molecule specific to a select subset of tissues in mice and humans.
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影响因子：
--
作者：
Landuzzi L;Ianzano ML;Nicoletti G;Palladini A;Grosso V;Ranieri D;Dall'Ora M;Raschi E;Laranga R;Gambarotti M;Picci P;De Giovanni C;Nanni P;Lollini PL
通讯作者：
Lollini PL
影响因子：
1.5
作者：
BLACKWELL, BN;BUCCI, TJ;TURTURRO, A
通讯作者：
TURTURRO, A
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
3.7
作者：
Hinkal G;Parikh N;Donehower LA
通讯作者：
Donehower LA
影响因子：
30.8
作者：
Liu, G;Parant, JM;Lozano, G
通讯作者：
Lozano, G