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Tumor-released exosomal circular RNA PDE8A promotes invasive growth via the miR-338/MACC1/MET pathway in pancreatic cancer
Ist Teil von
Cancer letters, 2018-09, Vol.432, p.237-250
Ort / Verlag
Ireland: Elsevier B.V
Erscheinungsjahr
2018
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
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.
•High level of circ-PDE8A is associated with tumor progression and prognosis.•Circ-PDE8A promotes the invasive growth via miR-338/MACC1/MET pathway.•Tumor released exosomes could enter into blood circulation and be detected.•Plasma exosomal circ-PDE8A is correlated to tumor invasion of PDAC patients.