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Proteomic analysis reveals the pro-proliferative role of the LIN28B/HMGA2 axis in hepatoblastoma
Jia Shi1, Yangkun Wu1, Cheng Cheng1
1Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Background:
Hepatoblastoma (HB) is the most common malignant liver tumor in pediatric patients. Even though the 5-year survival rate of HB patients has reached 80%, the prognosis in patients with high-risk features remain poor. This study aimed to establish the proteomic signature of HB to discover novel biomarkers and therapeutic targets.
Methods:
HPLC-MS/MS coupled with bioinformatic analyses were performed to identify the differentially expressed proteins and related GO/KEGG pathways in HB tumor tissues. Molecular biology experiments in HepG2 and Huh6 cells were conducted to validate findings of proteomic results.
Results:
Comparison of protein abundance profiles between HB tumors and normal adjacent liver tissues revealed high expression of HMGA2, IGFBP1, and LIN28B in HBs. GO/KEGG enrichment and protein-protein interaction analyses showed activation of RNA processing and the LIN28B/HMGA2 axis in HB tissue samples. Cellular and biochemical experiments confirmed that LIN28B expression was positively correlated with that of HMGA2, and that both promoted cell proliferation and tumor progression in the HB cell lines HepG2 and HUH6.
Conclusions:
In this study, we mapped the protein abundance profile of HB, identified a possible regulatory role and therapeutic potential of the LIN28B/HMGA2 axis, and provided database and foundation for future studies.
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