TRIM29 acts as a potential senescence suppressor with epigenetic activation in nasopharyngeal carcinoma.
TRIM29 acts as a potential senescence suppressor with epigenetic activation in nasopharyngeal carcinoma.
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作者：
以DNA甲基化为标志的表观遗传学改变是鼻咽癌早期发生的常见事件。我们鉴定了TRIM29在NPC细胞系和组织中是低甲基化和过表达的。TRIM29基因沉默不仅限制了鼻咽癌细胞的生长，而且沿着活性氧的积累，导致细胞衰老。从机制上讲，我们发现TRIM 29与电压依赖性阴离子选择性通道1（VDAC 1）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，高水平的TRIM29表达与晚期临床阶段相关。此外，我们在患者鼻咽拭子DNA中检测到TRIM29的低甲基化。我们的研究结果表明，TRIM29依赖于VDAC 1诱导线粒体自噬，并通过减少ROS来防止细胞衰老。检测鼻咽拭子DNA中异常甲基化的TRIM29可能是一种有希望的早期发现鼻咽癌的策略。TRIM29在鼻咽癌中低甲基化和过表达。TRIM29与VDAC 1结合，通过活性氧调节细胞衰老。在鼻咽拭子DNA中检测异常甲基化的TRIM29可能是一种有希望的早期检测鼻咽癌的策略。
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. TRIM29 is hypomethylated and overexpressed in nasopharyngeal carcinoma. TRIM29 combines with VDAC1 to regulate cellular senescence through reactive oxygen species. Detection of aberrantly methylated TRIM29 in the nasopharyngeal swab DNA could be a promising strategy for the early detection of nasopharyngeal carcinoma.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
48
作者：
Selbach, Matthias;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
64.5
作者：
Kuilman, Thomas;Michaloglou, Chrysiis;Peeper, Daniel S.
通讯作者：
Peeper, Daniel S.
影响因子：
6.4
作者：
Santin, AD;Zhan, FH;Pecorelli, S
通讯作者：
Pecorelli, S