MEG3 promotes liver cancer by activating PI3K/AKT pathway through regulating AP1G1

OBJECTIVE: This study aims to explore the biological function of maternally expressed gene 3 (MEG3) in liver cancer and the potential mechanism of phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) pathway in regulating proliferation and invasion of hepatoma cells.

PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was applied to examine the level of MEG3 in 72 pairs of liver cancer tissues and corresponding adjacent tissues. Expression levels of MEG3 and AP1G1 in hepatocellular carcinoma cell lines including SMMC-7721 and BEL-7402 were detected. After transfection of MEG3-siRNA or AP1G1 overexpression plasmid, the proliferative and invasive abilities of hepatoma cells were detected through cell counting kit-8 (CCK-8) and cell invasion assay. The effects of MEG3 and AP1G1 on the cell cycle of hepatoma cell lines were examined using flow cytometry. Western blot was conducted to estimate the changes in the protein levels of AP1G1, p-PI3K, p-AKT and VEGF before and after transfection.

RESULTS: The level of MEG3 in hepatoma cancer tissues and cell lines was significantly reduced, especially in patients with advanced liver cancer. Knockdown of MEG3 significantly promoted proliferation and invasion of hepatoma cells, but accelerated cell cycle. Western blot analysis revealed that knockdown of MEG3 reduced the level of AP1G1 and activated the PI3K/AKT pathway. In addition, rescue experiments demonstrated that overexpression of AP1G1 partially reversed the promotive effect of lowly-expressed MEG3 on cell proliferation and invasion, suggesting that low expression of MEG3 may activate PI3K/AKT pathway by inhibiting AP1G1 expression.

CONCLUSIONS: Low expression of MEG3 could promote the proliferative and invasive abilities of hepatoma cells and accelerate cell cycle. The mechanism may be related to the inhibition of AP1G1 expression and activation of PI3K/AKT pathway.

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