PHF19 activates hedgehog signaling and promotes tumorigenesis in hepatocellular carcinoma

Journal Article · Wed Sep 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112690· OSTI ID:23195542

Xiaoyun, Shi ^[1]; Yuyuan, Zi ^[2]; Jie, Xing ^[3]; Yingjie, Nie ^[4]; Qing, Xie ^[5]; Yuezhen, Deng ^[2]; Haiguang, Xin ^[5]

---

1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032 (China)
2. Xiangya Cancer Center, Xiangya Hospital, Central South University, Changsha, 410008 (China)
3. Department of Biobank, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030 (China)
4. NHC Key Laboratory of Pulmonary Immune-related Diseases, Guizhou Provincial People's Hospital, Guiyang, 550002 (China)
5. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025 (China)

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{sup F/F}) 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.

• OSTI ID: 23195542
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 406; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGAR
BIOLOGICAL FUNCTIONS
HEPATOMAS
HYDRODYNAMICS
LIGASES
MICE