Long noncoding RNA GMAN promotes hepatocellular carcinoma progression by interacting with eIF4B

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Gastric cancer metastasis associated long noncoding RNA (GMAN) is implicated in gastric cancer metastasis.
• The role and mechanisms of GMAN in hepatocellular carcinoma (HCC) remain largely unknown.

Purpose of the Study:

• To investigate the role and underlying mechanisms of GMAN in the progression of hepatocellular carcinoma (HCC).

Main Methods:

• Quantitative real-time PCR to assess GMAN expression in HCC tissues.
• In vitro and in vivo experiments involving GMAN knockdown and overexpression.
• Western blotting and co-immunoprecipitation to analyze protein interactions and phosphorylation.
• Assessment of apoptosis, proliferation, migration, and invasion.

Main Results:

• GMAN was significantly overexpressed in HCC tissues and associated with poor prognostic factors (vascular invasion, high TNM stage, short survival).
• GMAN knockdown induced apoptosis and suppressed HCC cell invasion and migration, while GMAN overexpression had opposite effects.
• GMAN promoted HCC cell viability primarily by inhibiting apoptosis.
• Mechanistically, GMAN binds to eukaryotic translation initiation factor 4B (eIF4B), promoting its phosphorylation and stability by inhibiting protein phosphatase 2A subunit B, leading to increased mRNA translation and anti-apoptosis protein expression.

Conclusions:

• GMAN acts as a crucial oncogenic long noncoding RNA in HCC progression.
• GMAN promotes HCC proliferation and metastasis by inhibiting apoptosis and enhancing cancer cell survival through the eIF4B pathway.
• GMAN represents a potential therapeutic target for HCC treatment.