Gastric cancer metastasis associated long noncoding RNA (GMAN), a long noncoding RNA, is associated with metastasis in gastric cancer. However, its underlying mechanisms in hepatocellular carcinoma (HCC) are unclear. We found that lncRNA-GMAN was significantly overexpressed in HCC tissues. GMAN expression is associated with vascular invasion, histological grade, tumor, node, metastasis (TNM) stage, short overall survival, and disease-free survival. Knockdown of GMAN induced apoptosis and suppressed invasive and migration potential in vitro and vivo, whereas ectopic GMAN expression produced the opposite effect. We also found that the inhibition of apoptosis, rather than promotion of proliferation, was responsible for GMAN-enhanced cellular viability. Mechanistic analyses indicated that GMAN directly combined with eukaryotic translation initiation factor 4B (eIF4B) and promoted its phosphorylation at serine-422 by preventing eIF4B binding and dephosphorization of the protein phosphatase 2A subunit B. The results demonstrated the stability of p-eIF4B and the elevation of mRNA translation and anti-apoptosis-related protein expression, which further induced proliferation and metastasis of HCC. The current study demonstrates that GMAN regulates the progression of HCC by inhibiting apoptosis and promoting the survival of cancer cells.
Keywords: Apoptosis; Dephosphorylation; Metastasis; PP2A family; Post-transcriptional regulation.
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