MDM2 依赖的 Sirt1 降解是头颈癌中 Sirt6 介导的细胞死亡的先决条件。
MDM2-dependent Sirt1 degradation is a prerequisite for Sirt6-mediated cell death in head and neck cancers.
作者信息
Park Jung Je, Hah Young-Sool, Ryu Somi, Cheon So Young, Won Seong Jun, Lee Jong Sil, Hwa Jeong Seok, Seo Ji Hyun, Chang Hyo Won, Kim Seong Who, Kim Sang Yoon
机构信息
Department of Otolaryngology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, South Korea.
Biomedical Research Institute, Gyeongsang National University Hospital, Jinju, Republic of Korea.
出版信息
Exp Mol Med. 2021 Mar;53(3):422-431. doi: 10.1038/s12276-021-00578-y. Epub 2021 Mar 16.
Sirt6 is involved in multiple biological processes, including aging, metabolism, and tumor suppression. Sirt1, another member of the sirtuin family, functionally overlaps with Sirt6, but its role in tumorigenesis is controversial. In this study, we focused on cell death in association with Sirt6/Sirt1 and reactive oxygen species (ROS) in head and neck squamous cell carcinomas (HNSCCs). Sirt6 induced cell death, as widely reported, but Sirt1 contributed to cell death only when it was suppressed by Sirt6 via regulation of MDM2. Sirt6 and Sirt6-mediated suppression of Sirt1 upregulated ROS, which further led to HNSCC cell death. These results provide insight into the molecular roles of Sirt6 and Sirt1 in tumorigenesis and could therefore contribute to the development of novel strategies to treat HNSCC.
沉默调节蛋白6（Sirt6）参与多种生物学过程，包括衰老、代谢和肿瘤抑制。沉默调节蛋白家族的另一个成员沉默调节蛋白1（Sirt1）在功能上与Sirt6重叠，但其在肿瘤发生中的作用存在争议。在本研究中，我们聚焦于头颈部鳞状细胞癌（HNSCC）中与Sirt6/Sirt1及活性氧（ROS）相关的细胞死亡。如广泛报道的那样，Sirt6诱导细胞死亡，但只有当Sirt1通过MDM2的调控被Sirt6抑制时，它才会促进细胞死亡。Sirt6以及Sirt6介导的对Sirt1的抑制上调了ROS，进而导致HNSCC细胞死亡。这些结果为Sirt6和Sirt1在肿瘤发生中的分子作用提供了见解，因此可能有助于开发治疗HNSCC的新策略。
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