Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer

BACKGROUND: Circular RNAs (circRNAs) play an important role in the tumorigenesis of pancreatic cancer. However, the expression profiles and roles of circRNAs in pancreatic cancer remain largely unknown. METHODS: To identify differentially expressed circRNAs (DEcircRNAs) between pancreatic cancer and matched normal tissues, bioinformatics analysis was performed. Hsa_circ_0000069 was identified by 0.bioinformatics analysis. In addition, the level of hsa_circ_0000069 in pancreatic cancer tissues and cell lines, and pancreatic cancer cell-derived exosomes were assessed using RT-qPCR assay. RESULTS: The expression of hsa_circ_0000069 was markedly upregulated in pancreatic cancer tissues and cell lines. SCL/TAL1 interrupting locus (STIL) is the parent gene for hsa_circ_0000069, and its high expression was related to poor overall survival in patients with pancreatic cancer. In addition, downregulation of hsa_circ_0000069 markedly suppressed STIL expression, induced the apoptosis and cell cycle arrest, and inhibited the proliferation, migration and invasion in pancreatic cancer cells. Moreover, hsa_circ_0000069 knockdown inhibited the growth of xenograft pancreatic cancer tumors in vivo. Furthermore, human pancreatic duct epithelial cells (HPDE) are capable of internalizing SW1990 cell-derived exosomes, allowing the transfer of hsa_circ_0000069. Significantly, SW1990 cell-derived exosomes promoted the proliferation, migration and cell cycle progression of HPDE cells, whereas exosomes with downregulated hsa_circ_0000069 suppressed the proliferation, migration and cell cycle progression of HPDE cells, by suppressing STIL expression. CONCLUSION: Our results suggest that hsa_circ_0000069 knockdown could inhibit pancreatic cancer tumorigenesis and exosomes with downregulated hsa_circ_0000069 could suppress HPDE cell malignant transformation. Collectively, hsa_circ_0000069 might be a therapeutic target for the treatment of pancreatic cancer.