The gene trim7 encodes at least four isoforms Glycogenin-interacting protein 1 (GNIP1), GNIP2, GNIP3 and Tripartite motif containing 7 (TRIM7). GNIP1, the longest isoform, has been reported acting as an oncogene. However, it is very interesting that TRIM7, the shortest isoform, only 15 amino acids different from GNIP1 in C-terminal, acts in a completely different way from that of GNIP1 in our present study. TRIM7 expression was decreased in tumor compared with adjacent normal tissues, and the level of TRIM7 was negatively correlated with clinical stage of 94 patients with lung cancer. In vitro, TRIM7 dramatically inhibited the proliferation and migration of tumor cells, and promoted cell apoptosis. Further study showed that TRIM7 interacted with p65 via its C-terminal which is different from GNIP1. The interaction between TRIM7 and p65 promoted the ubiquitination of p65 and finally accelerated the degradation of p65 via 26S proteasome. In vivo, the tumor volume and weight were decreased by TRIM7 stable expression. Meanwhile, Ki67 was down-regulated, thyroid transcription factor 1 (TTF-1) and Caspase 3 were up-regulated in TRIM7 overexpression group in xenograft model. It is very impressive that TRIM7t (a truncated TRIM7 without C-terminal sequence that different with GNIP1) had little effect on the tumor growth in vivo. These findings highlight a curious mechanism for negative regulation of NF-kappa B signaling pathway by TRIM7 and demonstrate that TRIM7 would be a potential therapeutic target for lung cancer.

中文翻译：

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E3泛素连接酶TRIM7通过降解肺癌中的p65负调控NF-κB信号通路。

trim7基因编码至少四个同工型糖原蛋白相互作用蛋白1（GNIP1），GNIP2，GNIP3和包含7的Tripartite基序（TRIM7）。据报道，最长的同工型GNIP1起着癌基因的作用。然而，非常有趣的是，TRIM7是最短的同工型，在C端仅与GNIP1不同，只有15个氨基酸，其作用与本研究中的GNIP1完全不同。与周围的正常组织相比，肿瘤中的TRIM7表达降低，并且TRIM7的水平与94例肺癌患者的临床分期呈负相关。在体外，TRIM7显着抑制肿瘤细胞的增殖和迁移，并促进细胞凋亡。进一步的研究表明，TRIM7通过其C末端与p65相互作用，这不同于GNIP1。TRIM7和p65之间的相互作用促进了p65的泛素化，并最终通过26S蛋白酶体加速了p65的降解。在体内，通过TRIM7稳定表达降低了肿瘤的体积和重量。同时，在异种移植模型的TRIM7过表达组中，Ki67被下调，甲状腺转录因子1（TTF-1）和Caspase 3被上调。令人印象深刻的是，TRIM7t（一种不带C端序列的截短TRIM7，与GNIP1不同）对体内肿瘤的生长几乎没有影响。这些发现强调了TRIM7负调节NF-κB信号通路的奇怪机制，并表明TRIM7将成为肺癌的潜在治疗靶标。TRIM7稳定表达降低了肿瘤的体积和重量。同时，在异种移植模型的TRIM7过表达组中，Ki67被下调，甲状腺转录因子1（TTF-1）和Caspase 3被上调。令人印象深刻的是，TRIM7t（一种不带C末端序列的截短TRIM7，与GNIP1不同）对体内肿瘤的生长几乎没有影响。这些发现强调了TRIM7负调节NF-κB信号通路的奇怪机制，并表明TRIM7将成为肺癌的潜在治疗靶标。TRIM7稳定表达降低了肿瘤的体积和重量。同时，在异种移植模型的TRIM7过表达组中，Ki67被下调，甲状腺转录因子1（TTF-1）和Caspase 3被上调。令人印象深刻的是，TRIM7t（不带C末端序列的截短TRIM7，与GNIP1不同）对体内肿瘤的生长几乎没有影响。这些发现强调了TRIM7负调节NF-κB信号通路的奇怪机制，并表明TRIM7将成为肺癌的潜在治疗靶标。令人印象深刻的是，TRIM7t（一种不带C端序列的截短TRIM7，与GNIP1不同）对体内肿瘤的生长几乎没有影响。这些发现强调了TRIM7对NF-κB信号通路负调控的奇怪机制，并证明了TRIM7将成为肺癌的潜在治疗靶标。令人印象深刻的是，TRIM7t（一种不带C端序列的截短TRIM7，与GNIP1不同）对体内肿瘤的生长几乎没有影响。这些发现强调了TRIM7负调节NF-κB信号通路的奇怪机制，并表明TRIM7将成为肺癌的潜在治疗靶标。