Mechanism of LncRNA FOXC2-AC1 promoting lung cancer metastasis by regulating miR-107

Previous studies have shown that long non-coding RNA (lncRNA) FOXC2-AC1 is one of cancer-promoting genes. However, the role of FOXC2-AC1 in lung cancer (LCa) has not been reported. This study aimed to investigate the expression characteristics of FOXC2-AC1 in LCa, and to further explore the mechanism by which it accelerates the metastasis of LCa.

Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect the level of FOXC2-AC1 in 62 pairs of LCa tissues and adjacent normal tissues, and the relationship between FOXC2-AC1 and LCa pathological parameters as well as the prognosis of patients were analyzed. Meanwhile, FOXC2-AC1 level was further verified in LCa cells by qRT-PCR. In addition, FOXC2-AC1 knockdown and overexpression models were constructed using lentivirus in LCa cell lines including H1299 and SPCA1, and the effect of FOXC2-AC1 on the biological function of LCa cells was analyzed by cell counting kit-8 (CCK-8) test along with transwell invasion and migration assay. Finally, the potential mechanism was explored using Western blotting assay.

In this study, qRT-PCR results indicated that the expression level of FOXC2-AC1 in LCa was considerably higher than that in normal tissues, with statistically significant differences. Compared with patients with low expression of FOXC2-AC1, patients with high expression of FOXC2-AC1 had higher incidence of distant metastasis and lower overall survival rate. Compared with the control group, the cell proliferation, invasion and metastasis capacities of FOXC2-AC1 overexpressing group were considerably enhanced, while opposite results were observed in the FOXC2-AC1 silencing group. In addition, miR-107 expression was found significantly reduced no matter in LCa cell lines or in tissues and showed a negative correlation with FOXC2-AC1. Subsequently, luciferase reporter gene assay demonstrated that overexpression of miR-107 significantly attenuated the luciferase activity of the wild-type FOXC2-AC1 vector without reducing the activity of the mutant vector or empty vector, further proving that FOXC2-AC1 could be targeted by miR-107 through this binding site. In addition, rescue experiment also found that FOXC2-AC1 and miR-107 have mutual regulation, which jointly affected the malignant progression of LCa.

These studies indicate that LncRNA FOXC2-AC1 is notably upregulated in LCa and is significantly correlated with LCa distant metastasis as well as poor prognosis. Therefore, it is suggested that lncRNA FOXC2-AC1 may promote malignant progression of LCa through the mutual regulation of miR-107.