Abnormal regulation of centrosome components can induce chromosome instability and tumorigenesis. Centrosomal protein 63 (CEP63) is a vital member for assembling centrosome. Yet, the involvement of CEP63 in cancer pathogenesis remains unclear. Here we identify CEP63 as an important mediator for RNA-binding proteins (RBPs) to facilitate regulation on their RNA targets in colorectal cancer (CRC). We demonstrate that CEP63 protein is upregulated in a large cohort of colorectal cancer tissues and predicts poor prognosis, and USP36 is identified for stabilizing CEP63 by enhancing its K48-dependent deubiquitination. CEP63 overexpression promotes the proliferation and tumor growth of CRC cells in vitro and in vivo. Furthermore, we find that CEP63 can promote cancer stem-like cell properties by enhancing YAP1 expression through binding with and inhibiting the K63-ubiquitylation degradation of RBP FXR1 in CRC cells. Importantly, we further verify that the KH domain of FXR1 is necessary for the interaction between CEP63 and FXR1. Moreover, microtube motor proteins can form a complex with CEP63 and FXR1 to mediate the regulation of FXR1 on RNA targets. Additionally, we also confirm that CEP63 can bind and regulate multiple RBPs. In conclusion, our findings unveil an unrecognized CEP63/RBPs/RNA axis that CEP63 may perform as an adapter facilitating the formation of RBPs complex to regulate RNA progression and discover the role of CEP63 involved in signal transduction and RNA regulation, providing potential therapeutic target for CRC patients.

中心体成分的异常调节可诱导染色体不稳定和肿瘤发生。中心体蛋白 63 (CEP63) 是组装中心体的重要成员。然而，CEP63 在癌症发病机制中的作用仍不清楚。在这里，我们将 CEP63 鉴定为 RNA 结合蛋白 (RBP) 的重要介质，以促进对其 RNA 靶标在结直肠癌 (CRC) 中的调节。我们证明 CEP63 蛋白在一大群结直肠癌组织中上调并预测预后不良，并且 USP36 被鉴定为通过增强其 K48 依赖性去泛素化来稳定 CEP63。CEP63过表达在体外和体内促进CRC细胞的增殖和肿瘤生长。此外，我们发现CEP63可以通过与CRC细胞中RBP FXR1的K63泛素化降解结合并抑制其K63泛素化降解来增强YAP1的表达，从而促进癌症干细胞样细胞的特性。重要的是，我们进一步验证了 FXR1 的 KH 结构域对于 CEP63 和 FXR1 之间的相互作用是必需的。此外，微管运动蛋白可以与 CEP63 和 FXR1 形成复合物，以介导 FXR1 对 RNA 靶标的调节。此外，我们还确认 CEP63 可以结合和调节多个 RBP。总之，我们的研究结果揭示了一个未被识别的 CEP63/RBPs/RNA 轴，CEP63 可能作为一个衔接子促进 RBPs 复合物的形成以调节 RNA 进展，并发现 CEP63 在信号转导和 RNA 调节中的作用，提供潜在的治疗靶点结直肠癌患者。