Department of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
J Cell Mol Med. 2022 Dec;26(23):5755-5766. doi: 10.1111/jcmm.17583. Epub 2022 Nov 20.
The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.
WD40 重复结构域蛋白在许多疾病（包括癌症）中的作用已得到充分证实。然而，WD 重复结构域 48（WDR48）在肝细胞癌（HCC）中的作用及其分子基础仍有待进一步研究。在本研究中，我们报告 WDR48 在临床 HCC 样本中下调，并评估其表达与 HCC 临床特征之间的关系。体外实验表明，WDR48 可正向调节 HCC 细胞的增殖、侵袭和转移，体内实验表明，下调 WDR48 可显著抑制 HCC 细胞的致瘤性。机制上，WDR48 与原癌基因转录调节剂 c-Myc 结合，并通过介导其去泛素化稳定 c-Myc 表达，从而增强细胞增殖和 EMT 信号。我们的研究证明了 WDR48 的致癌作用，并表明 WDR48 可以成为 HCC 的一个重要靶点。
