A novel long non-coding RNA TTN-AS1/microRNA-589-5p/FOXPl positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines

摘要

Numerous reports have found that long non-coding (lnc) RNAs were associated with pancreatic cancer (PC) initiation and development. The lncRNA titin antisense RNA 1 (TTN-AS1) was identified as a tumor promoter in certain types of cancer; however, its role and mechanism in PC remain unclear. The aim of the present study was to investigate the role of TTN-AS1 in PC and elucidate the underlying mechanism. Reverse transcription-quantitative PCR analysis was performed to examine the mRNA expression level of TTN-AS1, microRNA(miR)-589-5p and forkhead box protein 1 (FOXP1). Knockdown experiments were performed to examine the effect of TTN-AS1 on PC cell proliferation, migration and invasion. Luciferase reporter assays validated the binding of miR-589-5p to TTN-AS1 and FOXP1. Chromatin immunoprecipitation and luciferase reporter assays confirmed the binding ability of FOXP1 to the TTN-AS 1 promoter. As a result, TTN-AS1 and FOXP1 were found to be upregulated in PC cell lines and tissues, while miR-589-5p was expressed at low levels. Knockdown experiments indicated the suppres-sive effect of TTN-AS 1 knockdown on cell proliferation, migration and invasion in PC cell lines. Further mechanistic research uncovered that TTN-AS 1 functioned as a molecular sponge for miR-589-5p and its mRNA expression level in PC tissues was inversely associated with that of miR-589-5p. Furthermore, miR-589-5p was confirmed to target FOXP1.