miR-451 inhibits proliferation and promotes apoptosis of lung cancer cells by regulating target gene PSMB8-NOS2 and activating PI3K/AKT/mTOR signaling pathway

Zhiliang Lv*, Yingjie Li, Zhidong Dan, Kai Shen

The First People’s Hospital of Yongkang, Yongkang 321300, PR China

Objective: To investigate the effect of miR-451 on inhibiting proliferation and promoting apoptosis of lung cancer cells by regulating target genes PSMB8 and NOS2 and thus activating the PI3K/AKT/mTOR signaling pathway.

Methods: Non-small cell lung cancer A549 cells were cultured in vitro, and the expression of miR-451 in A549 cells was detected by real-time quantitative PCR. A549 cells were transfected with the miR-451 mimic and miR-451 inhibitor and were divided into miR-451 over-expression group, the miR-451 inhibitor group, over-expression control group, and inhibitor control group. The cell proliferation rate was measured by the CCK-8 method. The apoptosis rate of each group was determined by flow cytometry, and the mRNA expressions of PSMB8 and NOS2 were detected by real-time quantitative PCR. The levels of PI3K, AKT, and mTOR protein were measured by western blot assay.

Results: The mRNA expression of miR-451 in lung cancer A549 cells was lower than that in normal lung cell lines, and the difference was statistically significant (P < 0.05). The cell proliferation rate of the miR-451 over-expression group was lower than that of the over-expression control group (P < 0.05), and that of the miR-451 inhibitor group was markedly higher than that of the inhibitor control group (P < 0.05). The apoptosis rate of the miR-451 over-expression group was remarkably higher than that of the over-expression control group (P < 0.05), and that of the miR-451 inhibitor group was significantly lower than that of the inhibitor control group (P < 0.05). The mRNA expressions of PSMB8 and NOS2 in the miR-451 over-expression group were lower than those in the over-expression control group (P < 0.05), and the mRNA expressions of PSMB8 and NOS2 in the miR-451 inhibitor group were significantly higher than those in the inhibitor control group (P < 0.05). The expressions of PI3K, AKT, and mTOR protein in the miR-451 over-expression group were markedly lower than those in the over-expression control group (P < 0.05), and the expressions of PI3K, AKT, and mTOR in the miR-451 inhibitor group were significantly higher than those in the inhibitor control group (P < 0.05).

Conclusion: Overexpression of miR-451 can inhibit the proliferation of lung cancer cells and promote cell apoptosis. Its mechanism may be related to the inhibition of targeted inflammation-related genes PSMB8 and NOS2, which further regulate the PI3K/AKT/mTOR signaling pathway.