PUBLICATION
-A novel peptide SMIM45-107aa promotes HCC progression via MTDH pathways and its anticancer peptide derivative
- Authors
- An, Y., Shi, X., Huang, W., Shang, M., Jin, G.Z.
- ID
- ZDB-PUB-251112-14
- Date
- 2025
- Source
- Journal of translational medicine 23: 12661266 (Journal)
- Registered Authors
- Keywords
- Hepatocellular carcinoma, Interaction protein MTDH, MGST1, SMIM45-107aa, SMIM45-107aa-derived peptide
- MeSH Terms
-
- Animals
- Antineoplastic Agents*/chemistry
- Antineoplastic Agents*/pharmacology
- Antineoplastic Agents*/therapeutic use
- Carcinoma, Hepatocellular*/drug therapy
- Carcinoma, Hepatocellular*/genetics
- Carcinoma, Hepatocellular*/metabolism
- Carcinoma, Hepatocellular*/pathology
- Cell Adhesion Molecules*/metabolism
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Disease Progression*
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Liver Neoplasms*/drug therapy
- Liver Neoplasms*/genetics
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Male
- Membrane Proteins*/metabolism
- Mice
- Mice, Nude
- Peptides*/chemistry
- Peptides*/pharmacology
- Peptides*/therapeutic use
- Proto-Oncogene Proteins c-akt/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- RNA-Binding Proteins/metabolism
- Signal Transduction*/drug effects
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 41219895 Full text @ J Transl Med
Citation
An, Y., Shi, X., Huang, W., Shang, M., Jin, G.Z. (2025) -A novel peptide SMIM45-107aa promotes HCC progression via MTDH pathways and its anticancer peptide derivative. Journal of translational medicine. 23:12661266.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping