PDF(Pubmed)
Abstract：
Epigenetic alterations marked by DNA methylation are frequent events during the early development of nasopharyngeal carcinoma (NPC). We identified that TRIM29 is hypomethylated and overexpressed in NPC cell lines and tissues. TRIM29 silencing not only limited the growth of NPC cells in vitro and in vivo, but also induced cellular senescence, along with reactive oxygen species (ROS) accumulation. Mechanistically, we found that TRIM29 interacted with voltage-dependent anion-selective channel 1 (VDAC1) to activate mitophagy clearing up damaged mitochondria, which are the major source of ROS. In patients with NPC, high levels of TRIM29 expression are associated with an advanced clinical stage. Moreover, we detected hypomethylation of TRIM29 in patient nasopharyngeal swab DNA. Our findings indicate that TRIM29 depends on VDAC1 to induce mitophagy and prevents cellular senescence by decreasing ROS. Detection of aberrantly methylated TRIM29 in the nasopharyngeal swab DNA could be a promising strategy for the early detection of NPC.
摘要：
以DNA甲基化为标志的表观遗传改变是鼻咽癌（NPC）早期发展过程中的常见事件。我们确定TRIM29在NPC细胞系和组织中低甲基化和过表达。TRIM29沉默不仅限制了NPC细胞在体外和体内的生长，而且还诱导细胞衰老，随着活性氧（ROS）的积累。机械上,我们发现TRIM29与电压依赖性阴离子选择性通道1（VDAC1）相互作用以激活线粒体自噬清除受损的线粒体，这是ROS的主要来源。在NPC患者中，TRIM29的高水平表达与晚期临床阶段相关.此外，我们检测到患者鼻咽拭子DNA中TRIM29的低甲基化。我们的发现表明，TRIM29依赖于VDAC1诱导线粒体自噬，并通过减少ROS来防止细胞衰老。在鼻咽拭子DNA中检测异常甲基化的TRIM29可能是早期检测NPC的有希望的策略。
