WITHDRAWN: Stromal Cell-Derived Factor 1 Secreted by Cancer- Associated Fibroblasts Promotes lncRNA Xist through CXCR4 and Facilitates Invasion and Metastasis of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

Objective: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death. Cancer-associated fibroblasts (CAFs) promote NSCLC progression. This study investigated the effect of CAFs on NSCLC. Methods: CAFs and normal fibroblasts (NFs) were isolated and identified. SDF-1 expression in the blood of NSCLC patients was measured. Medium supernatant of CAFs or NFs was co-cultured with A549 or H1299 cells. Cell invasion and migration was assessed. Expressions 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 over-expression on H1299 was evaluated. Lung metastasis experiment was conducted and metastatic nodules were calculated. Results: SDF-1 was highly-expressed in NSCLC patients and CAFs. CAFs promoted the invasion and metastasis of NSCLC cells by secreting SDF-1. CAFs increased CXCR4 and Xist in NSCLC cells. SDF-1 knockdown or ADM3100 decreased CXCR4 and Xist expressions. Silencing Xist reduced the promoting effect of CAFs on NSCLC. Moreover, Xist targeted miR-15a-5p to regulate MMP3. Over-expression of miR-15a-5p promoted the invasion and migration of NSCLC cells. CAFs caused more metastatic nodules and elevated SDF-1, CXCR4, MMP3, N-cadherin and XIST levels, and lowered E-cadherin and miR-15a-5p levels. SDF-1 down-regulation in CAFs averted the effect of CAFs. Conclusion: SDF-1 secreted by CAFs promotes lncRNA Xist through CXCR4, and Xist targets miR-15a-5p to regulate MMP3, thus promoting the invasion and metastasis of NSCLC.