Stromal cell-derived factor 1 secreted by cancer-associated fibroblasts promotes lncRNA Xist through CXCR4 and facilitates invasion and metastasis of non-small cell lung cancer

Abstract Cancer-associated fibroblasts (CAFs) abundantly exist in NSCLCs and promote tumor progression in most solid tumors. This study investigated the effect of CAFs on NSCLC. CAFs and normal fibroblasts (NFs) were isolated and identified. CAFs or NFs were cocultured with NSCLCs cells. Cell invasion and migration, and expression of E-cadherin, N-cadherin, SDF-1, CXCR4 and Xist were measured. SDF-1/CXCR4 axis inhibitor ADM3100 or low expression of Xist was added to verify the invasion and metastasis of NSCLC. The binding relationships of Xist, miR-15a-5p and MMP3 were analyzed. The effect of miR-15a-5p overexpression on H1299 was evaluated. Finally, lung metastasis experiment was carried out in vivo. CAFs promoted the invasion and EMT of NSCLC cells by secreting SDF-1. CAFs increased CXCR4 and Xist expressions in NSCLC cells. SDF-1 knockdown or ADM3100 decreased CXCR4 and Xist expressions. Silencing Xist reduced the promotion of CAFs on NSCLC. Xist targeted miR-15a-5p to regulate MMP3. Overexpression of miR-15a-5p promoted the invasion and EMT of NSCLC cells. CAFs caused more metastatic nodules and elevated SDF-1, CXCR4, MMP3 and XIST levels, and lowered miR-15a-5p level. Collectively, SDF-1 secreted by CAFs promotes lncRNA Xist through CXCR4, and Xist targets miR-15a-5p to regulate MMP3, thus promoting invasion and metastasis of NSCLC.