Cell-permeated peptide P-T3H2 inhibits malignancy on hepatocellular carcinoma through stabilizing HNF4α protein

• DOI: 10.1007/s12672-024-01661-2
• Publication Date: 2024-12-05T16:09:18Z
• Authors: Si-Han Wu; Meng-Chao Xiao; Fang Liu; Huan-Yu Hong; Chen-Hong Ding; Xin Zhang; Wei-Fen Xie
• Keywords: Tribbles homolog 3; Hepatocellular carcinoma; Research; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Hepatocyte nuclear factor 4α; Cell-permeated peptide; RC254-282

Hepatocyte nuclear factor 4α (HNF4α) is a key regulator of hepatocyte function and has strong therapeutic effect on hepatocellular carcinoma (HCC) by inducing the differentiation hepatoma cell into hepatocytes. Our previous study showed that Tribbles homolog 3 (TRIB3) directly interacts with promotes degradation HNF4α in non-alcoholic fatty liver disease (NAFLD). Disrupting TRIB3–HNF4α interaction cell-permeating peptide, called P-T3H2, stabilized protein. This aimed to assess anti-tumor impact P-T3H2 HCC. The expression TRIB3 was evaluated using western blot immunohistochemistry (IHC). Hepatic functions cellular senescence HCC cells were through periodic acid-Schiff (PAS) staining, acetylated low-density lipoprotein (ac-LDL) uptake senescence-associated β-galactosidase (SA-β-gal) activity respectively. RNA-Seq analysis performed identify differentially expressed genes Huh7 treated P-T3H2. malignancy assessed vitro vivo. exhibited negative correlation both human mouse tissues. administration significantly inhibited cells. Additionally, protein facilitated restoration hepatic demonstrated enhanced transcriptional Furthermore, effectively suppressed carcinogenesis progression mice. stabilization may be promising candidate for clinical application treatment