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

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. 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. 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. 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.

• Publication year

  2025

• Venue

  Journal of Translational Medicine

• Publication date

  2025-11-11

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s12967-025-07179-7PMID 41219895PMCID 12606820
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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