前列腺癌骨转移是前列腺癌（PCa）患者死亡的主要原因。然而，人们对潜在机制知之甚少。在这里，我们报告高水平的 RNF41 与转移性人类前列腺癌有关。 RNF41 沉默可抑制体内外前列腺癌细胞的生长、细胞迁移和侵袭。从机制上讲，我们发现 RNF41 诱导 MYO1C 的 K27 和 K63 连接的非典型多泛素化，以增强其稳定性并诱导肌动蛋白重塑，从而促进 PCa 骨转移。 RNF41 在转移性前列腺癌组织中显着上调，并与 MYO1C 表达呈正相关。此外，我们在动脉内注射骨转移异种移植模型中显示，通过抑制 RNF41 来靶向 MYO1C 稳定性可显着抑制 PCa 骨转移。总的来说，我们的研究结果表明 RNF41 是前列腺癌细胞生长和转移的重要调节因子，靶向 RNF41/MYO1C 可能是改善前列腺癌进展和转移的有价值的策略。© 2024。作者，获得 Springer Nature 独家许可有限的。

Prostate cancer bone metastasis is a predominant cause of death for prostate cancer (PCa) patients. However, the underlying mechanisms are poorly understood. Here, we report that high levels of RNF41 are associated with metastatic human prostate cancer. RNF41 silencing inhibits prostate cancer cell growth, cell migration and invasion in vitro and in vivo. Mechanistically, we identify that RNF41 induces K27- and K63-linked noncanonical polyubiquitination of MYO1C to enhance its stability and induce actin remodeling, which promotes PCa bone metastasis. RNF41 was significantly upregulated in metastatic prostate cancer tissues and positively associated with MYO1C expression. Furthermore, we show in intraarterial injected-bone metastasis xenograft model that targeting MYO1C stability by inhibition of RNF41 markedly suppressed PCa bone metastasis. Collectively, our findings identify RNF41 is an important regulator of prostate cancer cell growth and metastasis and targeting RNF41/MYO1C could be a valuable strategy to ameliorate prostate cancer progression and metastasis.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.