Long-chain non-coding RNA LINC00473 antagonist with liposomal nanoparticles as carrier targets for Keap1/Nrf2/ARE signaling pathway to promote lung cancer cell apoptosis

Abstract

There is a relationship between abnormal expression of LncRNA LINC00473 and lung cancer cell apoptosis. This study mainly explored the role and mechanism of LncRNA LINC00473 in lung cancer cell apoptosis. Lung cancer cell line A549 was taken and study groups were set as follows; negative control (NC) group, si-con group, si-LINC00473 group, miR-634 group, si-LINC00473+anti-miR-con group, and si-LINC00473+antimiR-634 group. The expressions of LncRNA LINC00473 and miR-634 were observed and changes of cell proliferation and apoptosis-related indicators (Cyclin D1, Cleaved-caspase-3, cell survival rate, apoptosis rate) after interfering with expression of LncRNA LINC00473 and miR-634 respectively. Compared to HT-ori3 cells, the expression of LncRNA LINC00473 was higher while that of miR-634 was lower. Compared with the other two groups, the expressions of LncRNA LINC00473, Cyclin D1 and cell survival rate were lowest in the si-LINC00473 group, while the expression and apoptosis rate of Cleaved-caspase-3 were highest. Compared to the other two groups, the expression of miR-634 and Cleaved-caspase-3 and apoptosis rate in the miR-634 group were highest, and the cell survival rate of Cyclin D1 was lowest (p < 0.05). LncRNA LINC00473 gene sequence and miR-634 gene 3′UTR 641–678 sequence have specific binding regions, and miR-634 is the target gene for LncRNA LINC00473. The fluorescence intensity of mutant plasmid was markedly higher than that of wild-type plasmid (p<0.05). Compared with si-con group, the si-LINC00473 and si-LINC00473+anti-miR-con groups had higher miR-634, Cleaved-caspase-3 and apoptosis rates, while the Cyclin D1, cell survival rate, Keap1, p-Nrf2, and P-ARE expressions were low, but the si-LINC00473+antimiR-634 group was opposite. The LncRNA LINC00473 targets the RNA binding to the miR-634, thereby up-regulating the miR-634 expression and down-regulating the Keap1 expression.The LncRNA LINC00473 also inhibits the Nrf2, ARE phosphorylation and Cyclin D1 expression, and also promotes Cleaved-caspase-3 expression, ultimately inducing lung cancer cell apoptosis and inhibiting cell proliferation.