HMBOX1 inhibits hepatocellular carcinoma progression via PTPN1 mediated AKT1 phosphorylation

Hepatocellular carcinoma (HCC) represents the most common form of primary liver cancer and is characterized by a significant rate of recurrence. However, there is still a lack of effective therapeutic methods. Accumulating evidence has highlighted the importance of homeobox containing 1 (HMBOX1) in tumorigenesis. However, the relationship between HMBOX1 expression and HCC remains unclear. In the present study, through the analysis of public databases and staining analysis of tissue microarrays, it was found that compared with normal tissues, HMBOX1 was significantly downregulated in tumor tissues. Furthermore, through analyses such as Cell Counting Kit‑8 assay, wound healing assay and colony formation, it was found that overexpression of HMBOX1 could inhibit cell proliferation and migration, while silencing of HMBOX1 promoted tumor biological characteristics in HCC cell lines. The molecular biological mechanism was explored by using proteomics combined with bioinformatics analysis and western blotting. Mechanistically, AKT1 was identified as a downstream effector of HMBOX1, and protein tyrosine phosphatase non‑receptor type 1 (PTPN1) signaling might mediate the regulation of AKT1 by HMBOX1. In vivo tumor‑bearing experiments also verified the function of the HMBOX1/PTPN1/AKT1 pathway in HCC development. Taken together, the present findings revealed a new HMBOX1/PTPN1/AKT1 axis that inhibits tumor progression and provides new candidate therapy targets for HCC.