解析 CD24 在肝细胞癌中的作用：失活 Hippo 信号和 SOX4 介导的调控涉及其中。

Unraveling the role of CD24 in Hepatocellular carcinoma: Involvement of inactivated Hippo signaling and SOX4-mediated regulation.

机构信息

School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China; Zhejiang Provincial Engineering Research Centre for Key Technology of Diagnostic Testing, Hangzhou, China; Zhejiang Provincial Key Laboratory of Biomarkers and In Vitro Diagnostics Translation, Hangzhou, China.

Department of Clinical Laboratory, University-Town Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2024 Apr;1870(4):167117. doi: 10.1016/j.bbadis.2024.167117. Epub 2024 Mar 8.

DOI:10.1016/j.bbadis.2024.167117

PMID:38462024

Abstract

Hepatocellular carcinoma (HCC) is a prevalent type of liver cancer, and CD24 gene is reportedly involved in HCC progression. However, the precise regulatory mechanisms of CD24 in HCC remain unclear. In this study, we established a primary HCC mouse model and observed that CD24, induced by inactivation of the Hippo pathway, was highly expressed in HCC. Using a systematic molecular and genomic approach, we identified the Hippo-YAP1-SOX4 pathway as the mechanism through which YAP1 induces CD24 upregulation in HCC cells. CD24 knockdown significantly attenuated YAP1 activation-induced HCC. These findings shed light on the link between CD24 and HCC progression, particularly in the Hippo-inactivated subclass of HCC. Therefore, CD24 may serve as a potential target for specific treatment of this HCC subclass.

摘要

肝细胞癌（HCC）是一种常见的肝癌类型，据报道 CD24 基因参与 HCC 的进展。然而，CD24 在 HCC 中的精确调控机制尚不清楚。在本研究中，我们建立了一个原发性 HCC 小鼠模型，并观察到 Hippo 通路失活诱导的 CD24 在 HCC 中高表达。通过系统的分子和基因组方法，我们确定了 Hippo-YAP1-SOX4 通路是 YAP1 在 HCC 细胞中诱导 CD24 上调的机制。CD24 敲低显著减弱了 YAP1 激活诱导的 HCC。这些发现揭示了 CD24 与 HCC 进展之间的联系，特别是在 Hippo 失活的 HCC 亚类中。因此，CD24 可能成为针对这种 HCC 亚类的特定治疗的潜在靶点。