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Sirt5 对于 Braf 介导的体内皮肤黑色素瘤的发展和生长是可有可无的。

Sirt5 is dispensable for Braf -mediated cutaneous melanoma development and growth in vivo.

机构信息

Department of Biomedical Sciences, Cornell University, Ithaca, New York.

出版信息

Exp Dermatol. 2019 Jan;28(1):83-85. doi: 10.1111/exd.13845.

Abstract

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf -mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr ; Braf ; Pten ) to Sirt5 knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5 mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf -mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.

摘要

Sirt5 通过改变赖氨酸去琥珀酰化等翻译后修饰来调控线粒体蛋白,这一点已广为人知。虽然 Sirt5 作为肿瘤促进剂或抑制剂,或者在化疗耐药性方面的作用在其他癌症中已有相关报道,但 Sirt5 在皮肤黑色素瘤中的作用尚未得到充分研究。因此,为了确定 Sirt5 是否对 Braf 介导的黑色素瘤形成和/或疾病进展是必需的,我们将一种基因工程鼠黑色素瘤模型(Tyr ; Braf ; Pten )与 Sirt5 敲除动物进行了杂交。此外,我们还在 Sirt5 鼠黑色素瘤细胞中测试了与选择性 BRAF(V600E)抑制剂的协同作用。综上所述,本报告表明,在这些模型中,Sirt5 对于 Braf 介导的皮肤黑色素瘤的体内形成和生长并非必需,也不能提高对选择性 BRAF 抑制剂的敏感性。

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