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.

中文翻译：

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长的非编码RNA GMAN通过与eIF4B相互作用促进肝癌的进展。

胃癌转移相关的长非编码RNA（GMAN）（长非编码RNA）与胃癌的转移相关。然而，其在肝细胞癌（HCC）中的潜在机制尚不清楚。我们发现lncRNA-GMAN在肝癌组织中明显过表达。GMAN表达与血管浸润，组织学分级，肿瘤，淋巴结转移（TNM）阶段，总体生存期短和无病生存期相关。敲低GMAN诱导细胞凋亡，并在体外和体内抑制了侵袭和迁移的潜力，而异位GMAN表达产生相反的作用。我们还发现抑制凋亡而不是促进增殖是造成GMAN增强细胞活力的原因。机理分析表明，GMAN直接与真核翻译起始因子4B（eIF4B）结合，并通过阻止eIF4B结合和蛋白磷酸酶2A亚基B的去磷酸化而促进了其在丝氨酸422处的磷酸化。结果证明了p-eIF4B的稳定性和升高mRNA的翻译和抗凋亡相关蛋白的表达，进一步诱导肝癌的增殖和转移。目前的研究表明，GMAN通过抑制细胞凋亡和促进癌细胞存活来调节HCC的进程。结果证明p-eIF4B的稳定性以及mRNA翻译和抗凋亡相关蛋白表达的升高，这进一步诱导了HCC的增殖和转移。目前的研究表明，GMAN通过抑制细胞凋亡和促进癌细胞存活来调节HCC的进程。结果证明p-eIF4B的稳定性以及mRNA翻译和抗凋亡相关蛋白表达的升高，这进一步诱导了HCC的增殖和转移。当前的研究表明，GMAN通过抑制细胞凋亡和促进癌细胞存活来调节HCC的进程。