Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer

Z Li, WU Yanfang, J Li, P Jiang, T Peng, K Chen… - Cancer letters, 2018 - Elsevier
Z Li, WU Yanfang, J Li, P Jiang, T Peng, K Chen, X Zhao, Y Zhang, P Zhen, J Zhu, X Li
Cancer letters, 2018Elsevier
Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in
different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA
in pancreatic ductal adenocarcinoma (PDAC) tumor progression remain unclear. Here, we
identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray
analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A
expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of …
Abstract
Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA in pancreatic ductal adenocarcinoma (PDAC) tumor progression remain unclear. Here, we identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of PDAC patients. Further study revealed that circ-PDE8A promotes the invasive growth of PDAC cells via upregulating MET. Circ-PDE8A acts as a ceRNA for miR-338 to regulate MACC1 and stimulates invasive growth via the MACC/MET/ERK or AKT pathways. We further imaged the exosome communication between tumor cells and identified the tumor secreted exosomes in blood circulation. Finally, we analyzed the circ-PDE8A expression in plasma exosomes of PDAC patients and found that exosomal circ-PDE8A was associated with progression and prognosis in PDAC patients. Thus, circ-PDE8A may play an important role in tumor invasion, and exosomal circ-PDE8A may be a useful marker of PDAC diagnosis or progression.
Elsevier