I型干扰素具有抗增殖和抗癌活性，但其在癌症中的详细调节机制尚未完全阐明。 RNA结合蛋白是基因调控的主要协调者，与肿瘤进展密切相关。在这里，我们发现 RNA 结合蛋白 RBM45 的上调与乳腺癌的不良预后相关。 RBM45 的消耗可抑制培养细胞和异种移植小鼠模型中的乳腺癌进展。从机制上讲，RBM45 消除通过调节 I 型干扰素信号传导，特别是通过提高 IFN-β 的产生来抑制乳腺癌进展。重要的是，RBM45 将 TRIM28 招募到 IRF7 并刺激其 SUMO 化，从而抑制 IFNB1 转录。 RBM45 的缺失通过减少 TRIM28 和 IRF7 之间的相互作用来减少 IRF7 的 SUMOylation，从而促进 IFNB1 转录，从而抑制乳腺癌进展。总而言之，我们的发现揭示了 RBM45 在调节 I 型干扰素信号传导和癌症侵袭进展中的重要作用，表明 RBM45 作为乳腺癌的潜在治疗靶点。版权所有 © 2024。由 Elsevier B.V. 出版。

Type I interferons exhibit anti-proliferative and anti-cancer activities, but their detailed regulatory mechanisms in cancer have not been fully elucidated yet. RNA binding proteins are master orchestrators of gene regulation, which are closely related to tumor progression. Here we show that the upregulated RNA binding protein RBM45 correlates with poor prognosis in breast cancer. Depletion of RBM45 suppresses breast cancer progression both in cultured cells and xenograft mouse models. Mechanistically, RBM45 ablation inhibits breast cancer progression through regulating type I interferon signaling, particularly by elevating IFN-β production. Importantly, RBM45 recruits TRIM28 to IRF7 and stimulates its SUMOylation, thereby repressing IFNB1 transcription. Loss of RBM45 reduced the SUMOylation of IRF7 by reducing the interaction between TRIM28 and IRF7 to promote IFNB1 transcription, leading to the inhibition of breast cancer progression. Taken together, our finding uncovers a vital role of RBM45 in modulating type I interferon signaling and cancer aggressive progression, implicating RBM45 as a potential therapeutic target in breast cancer.Copyright © 2024. Published by Elsevier B.V.