Effect of LncRNA IGFL2-AS1 on the Malignant Biological Behavior of Lung Cancer Cells by Regulating the miR-138-5p/FOXP4 Axis

This research was to investigate the effect of LncRNA (long non coding RNA) IGFL2-AS1 (insulin-like growth factor family member 2 antisense RNA 1) on the malignant biological behavior of lung can cer cells by regulating the miR-138-5p/FOXP4 (forkhead protein 4) axis. This research adopted a total of 55 lung cancer tissues and paracancer tissue specimens collected from June 2023 to December 2024 in Cangzhou People’s Hospital. This research adopted human normal epithelial lung cells (BEAS-2B) and lung cancer cell lines (A549, NCI-H1975, PC-9). A549 cells were assigned into Control group, sh-NC group, sh-IGFL2-AS1 group, sh-IGFL2 AS1+anti-NC group, and sh-IGFL2-AS1+anti-miR-138-5p group randomly. qRT-PCR was applied to detect the expression levels of LncRNA IGFL2-AS1, miR-138-5p, and FOXP4 mRNA in cells. The relationship between LncRNA IGFL2-AS1 and miR-138-5p, between miR-138-5p and FOXP4 were detected by dual luciferase as say. Cell proliferation in each group was detected by CCK8 and clone formation assays. Transwell was applied to detect cell migration and invasion in each group. Flow cytometry was applied to detect apoptosis in each group. Western blot was applied to detect the expression levels of E-cadherin, Vimentin, Bcl-2, Bax, and FOXP4 proteins in each group. Nude mice were divided into control group (subcutaneous injection of 106 sh-NC group cells) and experimental group (subcutaneous injection of 106 sh-IGFL2-AS1 group cells). The effect of LncRNA IGFL2 AS1 deletion on the growth of lung cancer and the expression of LncRNA IGFL2-AS1, miR-138-5p and FOXP4 mRNA were verified in nude mice. This research concluded that qRT-PCR results showed that compared with the paracancer tissue, the expression of LncRNA IGFL2-AS1 and FOXP4 mRNA in lung cancer tissues were increased, while the expression of miR-138-5p was decreased (P<0.05). Compared with normal epithelial lung cells, the relative expression levels of LncRNA IGFL2-AS1 and FOXP4 mRNA in lung cancer cell lines (A549, NCI-H1975, PC-9) increased, while the relative expression level of miR-138-5p decreased. The expression lev els of LncRNA IGFL2-AS1, miR-138-5p, and FOXP4 mRNA in A549 cells showed the most great differences (P<0.05), therefore A549 cells were selected for subsequent experiments. Dual luciferase assay showed that after transfection with WT-IGFL2-AS1 and WT-FOXP4, compared with the mimic-NC group, the luciferase activity of the miR-138-3p mimic group decreased (P<0.05). Compared with the sh-NC and Control groups, the survival rate, clone number, migration number, invasion number, FOXP4 mRNA level, and the protein expression levels of Vimentin, Bcl-2, FOXP4 of A549 cells in the sh-IGFL2-AS1 group decreased, while the apoptosis rate, miR 138-5p, the levels of E-cadherin, and Bax protein increased (P<0.05). Compared with the sh-IGFL2-AS1 group and sh-IGFL2-AS1+anti-NC group, the survival rate, clone number, migration number, invasion number, FOXP4 mRNA level, and Vimentin, Bcl-2, FOXP4 protein expression levels of A549 cells in the sh-IGFL2-AS1+anti miR-138-5p group increased, while the apoptosis rate, miR-138-5p, E-cadherin, and Bax protein expression levels decreased (P<0.05). The tumor mass and volume, LncRNA IGFL2-AS1 and FOXP4 mRNA expressions in the experimental group were lower than those of the control group, and miR-138-5p expression was higher than that in control group (P<0.05). In summary, interfering with LncRNA IGFL2-AS1 may affect the miR-138-5p/FOXP4 axis, thereby inducing apoptosis of lung cancer cells, blocking the migration, proliferation and invasion of lung cancer cells, and ultimately reversing their malignant phenotype.

CSTR: 32200.14.cjcb.2025.10.0013