CircGNAO1 strengthens its host gene GNAO1 expression for suppression of hepatocarcinogenesis

Area of Science:

• Oncology
• Molecular Biology
• Epigenetics

Background:

• Hepatocellular carcinoma (HCC) is a common primary liver cancer.
• Guanine nucleotide-binding protein, α-activating activity polypeptide O (GNAO1) is underexpressed in HCC.
• The role of GNAO1-derived circular RNA (circGNAO1) in HCC remains unclear.

Purpose of the Study:

• To investigate the expression and function of circGNAO1 in HCC.
• To elucidate the molecular mechanisms underlying circGNAO1's role in HCC progression.
• To explore the relationship between circGNAO1, GNAO1, and DNA methyltransferase 1 (DNMT1).

Main Methods:

• Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot for gene and protein expression analysis.
• Functional assays to assess HCC cell proliferation, cell cycle, and senescence.
• Mechanism assays to examine interactions between circGNAO1, GNAO1, and DNMT1, including bisulfite sequencing PCR (BSP) for methylation analysis.

Main Results:

• CircGNAO1 is downregulated in HCC tissues and positively correlated with GNAO1 expression.
• Overexpression of circGNAO1 inhibits HCC cell proliferation, induces cell cycle arrest, and promotes cellular senescence.
• CircGNAO1 enhances GNAO1 transcription by sequestering DNMT1, leading to increased GNAO1 expression in HCC cells.

Conclusions:

• CircGNAO1 acts as a tumor suppressor in HCC.
• CircGNAO1 upregulates GNAO1 expression, thereby inhibiting hepatocarcinogenesis.
• CircGNAO1 may serve as a potential therapeutic target for HCC.