PHF19 激活 hedgehog 信号通路并促进肝癌发生。

PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma.

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.

Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008, China.

出版信息

Exp Cell Res. 2021 Sep 1;406(1):112690. doi: 10.1016/j.yexcr.2021.112690. Epub 2021 Jun 12.

DOI:10.1016/j.yexcr.2021.112690

PMID:34129846

Abstract

Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (Myc) using the hydrodynamic method inhibited tumorigenesis and improved survival. Taken together, these results demonstrate that PHF19 promotes the growth of HCC cells by activating the Hedgehog signaling pathway.

摘要

Hedgehog-Gli1 信号的异常激活和 Gli1 在肝细胞癌 (HCC) 中的积累经常被观察到。然而，导致这种信号通路过度激活的机制尚不完全清楚。在这项研究中，我们表明短型 PHF19 与 β-TrCP（Gli1 的 E3 连接酶）相互作用，并且敲低 PHF19 可促进 Gli1 的泛素化。在一项生物学功能研究中，发现 PHF19 促进 HCC 细胞在液体培养和软琼脂中的生长。此外，使用水力方法在 HCC 小鼠模型 (Myc) 中敲除 PHF19 可抑制肿瘤发生并提高存活率。总之，这些结果表明 PHF19 通过激活 Hedgehog 信号通路促进 HCC 细胞的生长。