Transcriptomic changes associated with PCK1 overexpression in hepatocellular carcinoma cells detected by RNA-seq.

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Phosphoenolpyruvate carboxykinase 1 (PCK1) is crucial for gluconeogenesis and is downregulated in hepatocellular carcinoma (HCC).
• PCK1 overexpression inhibits hepatoma cell growth, but the mechanism is not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which PCK1 suppresses HCC cell growth.
• To identify signaling pathways affected by PCK1 overexpression in HCC.

Main Methods:

• Recombinant adenovirus vectors were used to overexpress PCK1 in Huh7 HCC cells.
• RNA-sequencing (RNA-Seq) identified differentially expressed genes (DEGs).
• Quantitative reverse transcription PCR (qRT-PCR) and Western blot validated gene and protein expression changes.

Main Results:

• PCK1 overexpression altered the expression of 180 upregulated and 316 downregulated genes.
• Pathway analysis revealed correlations between PCK1 and Wnt/TGF-beta signaling pathways.
• PCK1 overexpression decreased the expression of beta-catenin, a key Wnt pathway component, and inhibited tumor growth in vivo.

Conclusions:

• PCK1 overexpression downregulates oncogenic signaling pathways, including Wnt signaling, in HCC.
• PCK1 acts as a tumor suppressor in HCC by inhibiting beta-catenin expression.
• Targeting PCK1 may offer a novel therapeutic strategy for HCC treatment.