Long non-coding RNA ZFAS1 promotes pancreatic cancer proliferation and metastasis by sponging miR-497-5p to regulate HMGA2 expression

Abstract

AbstractThe lncRNA ZFAS1 plays a carcinogenic regulatory role in many human tumours, but it is rarely reported in pancreatic cancer. We identify the role and molecular mechanisms of ZFAS1 in pancreatic cancer. The expression of ZFAS1, miR-497-5p and HMGA2 in pancreatic cancer tissues was detected by qRT-PCR. Pancreatic cancer data in The Cancer Genome Atlas were also included in this study. CCK8, EdU, transwell and scratch wound assays were used to investigate the biological effects of ZFAS1 in pancreatic cancer cells. MS2-RIP, RNA pull-down, RNA-ChIP and luciferase reporter assays were used to clarify the molecular biological mechanisms of ZFAS1 in pancreatic cancer. The role of ZFAS1 in vivo was also confirmed via xenograft experiments. ZFAS1 was overexpressed in pancreatic cancer tissues. ZFAS1 promoted the growth and metastasis of pancreatic cancer cells, and miR-497-5p acted as a tumour suppressor gene in pancreatic cancer by targeting HMGA2. We also demonstrated that ZFAS1 exerts its effects by promoting HMGA2 expression through decoying miR-497-5p. We also found that ZFAS1 promoted the progression of pancreatic cancer in vivo by modulating the miR-497-5p/HMGA2 axis. In conclusion, this study revealed a new role for and the molecular mechanisms of ZFAS1 in pancreatic cancer, identifying ZFAS1 as a novel target for the diagnosis and treatment of pancreatic cancer.