TRIM65（含65的三联基序）作为典型的E3连接酶，参与抗病毒先天免疫的调节和某些肿瘤的发病机制。然而，TRIM65在肾细胞癌（RCC）中的作用及其潜在机制尚未确定。在这项研究中，我们将 TRIM65 确定为 RCC 中的一种新癌基因，它在体外和体内增强肿瘤细胞的增殖和贴壁依赖性生长能力。此外，我们发现TRIM65主要通过与BTG3（BTG抗增殖因子3）直接相互作用来调节RCC增殖，进而诱导K48连接的泛素化和随后通过K41氨基酸的降解。此外，TRIM65 通过降解 BTG3 缓解 G2/M 期细胞周期停滞并调节下游因子。进一步的研究表明，TRIM65 通过 TRIM65-BTG3-CyclinD1 轴发挥作用，临床样本 IHC 芯片数据表明 TRIM65 和 BTG3 之间存在负校正。总而言之，我们的研究结果表明，TRIM65 通过降解 BTG3 来调节细胞周期，从而促进 RCC 细胞增殖，这表明 TRIM65 可能是 RCC 治疗的一个有前景的靶标。© 2024。作者。

As a typical E3 ligase, TRIM65 (tripartite motif containing 65) is involved in the regulation of antiviral innate immunity and the pathogenesis of certain tumors. However, the role of TRIM65 in renal cell carcinoma (RCC) and the underlying mechanism has not been determined yet. In this study, we identified TRIM65 as a novel oncogene in RCC, which enhanced the tumor cell proliferation and anchorage-independent growth abilities both in vitro and in vivo. Moreover, we found that TRIM65-regulated RCC proliferation mainly via direct interaction with BTG3 (BTG anti-proliferation factor 3), which in turn induced the K48-linked ubiquitination and subsequent degradation through K41 amino acid. Furthermore, TRIM65 relieved G2/M phase cell cycle arrest via degradation of BTG3 and regulated downstream factors. Further studies revealed that TRIM65 acts through TRIM65-BTG3-CyclinD1 axis and clinical sample IHC chip data indicated a negative correction between TRIM65 and BTG3. Taken together, our findings demonstrated that TRIM65 promotes RCC cell proliferation via regulation of the cell cycle through degradation of BTG3, suggesting that TRIM65 may be a promising target for RCC therapy.© 2024. The Author(s).