Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma

Hang Song; Ji Ma; Zhixuan Bian; Shuhua Chen; Jiabei Zhu; Jing Wang; Nan Huang; Minzhi Yin; Fenyong Sun; Min Xu; Qiuhui Pan

doi:10.1038/s41392-019-0067-4

Global profiling of O-GlcNAcylated and/or phosphorylated proteins in hepatoblastoma

Signal Transduct Target Ther. 2019 Oct 11:4:40. doi: 10.1038/s41392-019-0067-4. eCollection 2019.

Authors

Hang Song^#¹, Ji Ma^#¹, Zhixuan Bian^#¹, Shuhua Chen², Jiabei Zhu¹, Jing Wang³, Nan Huang⁴, Minzhi Yin⁵, Fenyong Sun⁴, Min Xu³, Qiuhui Pan¹

Affiliations

¹ 1Department of Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, 200127 Shanghai, China.
² Department of Laboratory Medicine, Yunfu People's Hospital, 527300 Guangdong, China.
³ 3Department of Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, 200127 Shanghai, China.
⁴ 4Department of Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, 200072 Shanghai, China.
⁵ 5Department of Pathology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, 200127 Shanghai, China.

^# Contributed equally.

Abstract

O-linked-β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) and phosphorylation are critical posttranslational modifications that are involved in regulating the functions of proteins involved in tumorigenesis and the development of various solid tumors. However, a detailed characterization of the patterns of these modifications at the peptide or protein level in hepatoblastoma (HB), a highly malignant primary hepatic tumor with an extremely low incidence in children, has not been performed. Here, we examined O-GlcNAc-modified or phospho-modified peptides and proteins in HB through quantitative proteomic analysis of HB tissues and paired normal liver tissues. Our results identified 114 O-GlcNAcylated peptides belonging to 78 proteins and 3494 phosphorylated peptides in 2088 proteins. Interestingly, 41 proteins were modified by both O-GlcNAcylation and phosphorylation. These proteins are involved in multiple molecular and cellular processes, including chromatin remodeling, transcription, translation, transportation, and organelle organization. In addition, we verified the accuracy of the proteomics results and found a competitive inhibitory effect between O-GlcNAcylation and phosphorylation of HSPB1. Further, O-GlcNAcylation modification of HSPB1 promoted proliferation and enhanced the chemotherapeutic resistance of HB cell lines in vitro. Collectively, our research suggests that O-GlcNAc-modified and/or phospho-modified proteins may play a crucial role in the pathogenesis of HB.

Keywords: Epigenetics; Molecular medicine.

Publication types

Research Support, Non-U.S. Gov't