Circular RNA ADAM9 facilitates the malignant behaviours of pancreatic cancer by sponging miR-217 and upregulating PRSS3 expression

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 47; no. 1; pp. 3920 - 3928
• Main Authors: Xing, Chenju, Ye, Hua, Wang, Weiwei, Sun, Miaomiao, Zhang, Jianying, Zhao, Zhihua, Jiang, Guozhong
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.12.2019; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Cancer; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cell Transformation, Neoplastic; ceRNA; Circular RNA; Disease Progression; ERK signalling; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Silencing; Humans; Lymph nodes; Male; Metastases; Mice; microRNA; MicroRNAs - genetics; Neoplasm Invasiveness; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; prognosis; Ribonucleic acid; RNA; RNA, Circular - genetics; Serine; Serine proteinase; Signal transduction; Signal Transduction - genetics; Signaling; Trypsin - genetics; Tumors; Up-Regulation - genetics; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; ERK signalling; ceRNA; microRNA; prognosis; Pancreatic cancer; circular RNA
• ISSN: 2169-1401; 2169-141X
• DOI: 10.1080/21691401.2019.1671856

Pancreatic cancer (PC) is a highly lethal human cancer. We previously found that Serine protease 3 (PRSS3), as an oncogene, is significantly upregulated in PC. In this study, we aimed to investigate the potential mechanism of PRSS3 dysregulation in PC. In this research, low miR-217 and high circ-ADAM9 expression were found in PC tissues and cell lines, which was closely associated with advanced clinical stage and lymph node metastasis. Patients with low miR-217 or high circ-ADAM9 expression had shorter survival time than those with high miR-217 or low circ-ADAM9 expression. Functionally, manipulation of miR-217 and circ-ADAM9 expression showed opposite effects on cell proliferation, migration and invasion. Stepwise mechanism studies indicated that circ-ADAM9 alleviated the inhibitory effect of miR-217 on PRSS3 by directly sponging miR-217 to increase the expression level of PRSS3, resulting in the activation of ERK/VEGF signalling pathway. In vivo, circ-ADAM9 silencing or miR-217 overexpression evidently retarded the growth of tumour, and the combination of them exhibited an additive inhibitory effect on tumourigenicity. Briefly, the ceRNA regulatory network of circ-ADAM9/miR-217/PRSS3 plays a pivotal role in PC progression by the regulation of ERK/VEGF signalling pathway.