Work

–A novel peptide SMIM45-107aa promotes HCC progression via MTDH pathways and its anticancer peptide derivative

Year: 2025

Type: article

Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, and the treatment options are limited. Growing evidence shows that long non-coding RNAs (LncRNAs) encode peptides, suggesting that lncRNAs-derived peptides may play a role in HCC progression and explore their potential as therapeutic targets. METHODS: We used RNA-sequencing and bioinformatics analysis to identify a 107-amino acid peptide, SMIM45-107aa, encoded by LINC00634. The expression levels and prognostic significance of SMIM45-107aa in HCC tissues were assessed by immunohistochemistry (IHC) and Kaplan-Meier. Wound-healing and cell colony formation evaluate the effects of SMIM45-107aa on cell migration and proliferation. A mouse xenograft model was used to examine the tumor formation. Interactions between SMIM45-107aa and MTDH were explored and the effects on MTDH ubiquitination were investigated by immunoprecipitation. Proteomic analysis and Western blotting confirmed the mechanism of SMIM45-107aa effected HCC. Additionally, a short peptide, peptide 5 derived from SMIM45-107aa was analyzed by cell migration in SK-Hep1 cells and by zebrafish model. RESULTS: SMIM45-107aa was highly expressed in HCC tissues and associated with poor prognosis. It promoted cell migration and proliferation in vitro and tumor formation in vivo. SMIM45-107aa interacted with MTDH, inhibiting its ubiquitination and stabilizing the protein. Proteomic and Western blot analysis revealed that SMIM45-107aa upregulated MGST1 and phosphorylated AKT (pAKT). Importantly, peptide 5 inhibited SMIM45-107aa-induced cell migration and demonstrated anticancer activity in zebrafish models. CONCLUSION: We identified SMIM45-107aa, a novel peptide encoded by LINC00634, which promoted HCC progression via the MGST1-pAKT-MTDH axis. The derived peptide 5 exhibited anticancer activity, suggesting a potential therapeutic strategy for HCC.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-025-07179-7

Authors: Yan An, Xiangyang Shi, Wentao Huang, Mingyi Shang, Guang-Zhi Jin