Super enhancer-LncRNA SENCR promoted cisplatin resistance and growth of NSCLC through upregulating FLI1.

BACKGROUND: Super enhancer-lncRNA smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) were highly overexpressed in cisplatin-resistant A549/DDP cells, while the mechanism was unclear. METHODS: SE-lncRNA SENCR and FLI1 mRNA expression in A549/DDP cell, LAD tissues were detected. SENCR knockdown of A549/DDP cell and SENCR overexpression of cisplatin-sensitive A549 cell were constructed. Experiments of cell-confirmed function of SENCR and the correlation between SENCR and FLI1 were validated. RESULTS: The expression of SENCR and FLI1 mRNA in A549/DDP cell were both upregulated and mainly localized in the nucleus. Compared with DDP-sensitive tissues with disease relief, SENCR expression was higher in DDP-resistant tissues with disease progression from LAD. Knockdown of SENCR in A549/DDP reduced proliferation ability and cisplatin resistance, consistent with the decreased levels of proteins PCNA, MDMX, and P-gp. Besides, whatever without cisplatin or with 2 µg/ml cisplatin, knockdown of SENCR reduced the migration, invasion, and colony formation abilities of A549/DDP cell and promoted apoptosis. However, when SENCR was overexpressed in A549 cell, all above results were reversed. Mechanistically, FLI1 expression was reduced after knocking down SENCR, while overexpressing SENCR increased FLI1 expression. CONCLUSION: SE-LncRNA SENCR was upregulated in A549/DDP, which could promote cisplatin resistance and growth of NSCLC cell through upregulating FLI1 expression.