N-trans-Feruloyloctopamine Wakes Up BBC3, DDIT3, CDKN1A, and NOXA Signals to Accelerate HCC Cell Apoptosis

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• N-trans-Feruloyloctopamine (FO) previously demonstrated inhibition of hepatocellular carcinoma (HCC) malignant phenotypes via AKT and EMT pathways.
• The precise molecular targets and mechanisms underlying FO's anti-cancer effects require further elucidation.

Purpose of the Study:

• To identify specific molecular targets and elucidate the detailed mechanisms by which FO impacts HCC cells.
• To investigate the effects of FO on HCC cell proliferation and apoptosis.

Main Methods:

• RNA sequencing (RNA-Seq) was employed to screen gene expression changes in FO-treated Huh7 HCC cells.
• Real-time cell analysis and flow cytometry were used to assess proliferation and apoptosis.
• Bioinformatic analyses, including DAVID and KEGG pathway enrichment, were performed to identify regulated biological processes and signaling pathways.

Main Results:

• FO modulated 317 genes in Huh7 cells, with 188 upregulated and 129 downregulated.
• FO significantly impacted HCC cell proliferation and induced apoptosis.
• KEGG analysis revealed FO primarily regulates PI3K-AKT and apoptosis signaling pathways.
• Novel targets BBC3, DDIT3, NOXA, and CDKN1A were identified as crucial mediators of FO-induced apoptosis in HCC cells.

Conclusions:

• FO exacerbates HCC cell apoptosis through the regulation of BBC3, DDIT3, CDKN1A, and NOXA signaling pathways.
• FO presents a promising therapeutic strategy for liver cancer, with its identified targets offering new avenues for drug development.