Unveiling the role of UPF3B in hepatocellular carcinoma: Potential therapeutic target

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• RNA-binding proteins regulate critical cellular processes, including nucleotide metabolism and gene expression.
• UPF3B (UPF3B regulator of nonsense mediated mRNA decay) is implicated in various cancers, but its specific role in hepatocellular carcinoma (HCC) remains unclear.

Purpose of the Study:

• To investigate the role and mechanism of UPF3B in the progression of hepatocellular carcinoma (HCC).
• To identify potential therapeutic targets for HCC based on UPF3B's function.

Main Methods:

• Analysis of UPF3B expression levels in HCC patient samples.
• In vivo and in vitro experiments to assess the impact of UPF3B on HCC growth.
• Mechanistic studies involving RNA-binding assays, mRNA degradation analysis, and pathway activation assessments (PI3K/AKT/mTOR).
• Investigation of the transcriptional regulation of UPF3B by E2F transcription factor 6 (E2F6).

Main Results:

• UPF3B was significantly upregulated in HCC tissues and correlated with poor patient prognosis.
• UPF3B overexpression promoted HCC cell proliferation and tumor growth in both experimental models.
• UPF3B directly binds to PPP2R2C mRNA, leading to its degradation and subsequent activation of the PI3K/AKT/mTOR signaling pathway.
• E2F6 was identified as a direct transcriptional activator of UPF3B.

Conclusions:

• The E2F6/UPF3B/PPP2R2C signaling axis promotes HCC progression via the PI3K/AKT/mTOR pathway.
• UPF3B represents a potential diagnostic biomarker and therapeutic target for hepatocellular carcinoma.