uPAR is regulated via miR-561-3p and affects the progression and aggressiveness of CRC cells via the PI3K/AKT signaling pathway

Abstract

Abstract Urokinase plasminogen activator (uPA), the uPA receptor (uPAR) and plasminogen activator inhibitor type 1, constitute the plasminogen urokinase activation system that is hypothesized to be associated with the malignant biology of cancer cells. However, the regulation mechanism of uPAR expression in colorectal cancer (CRC) remains unclear. In the present study it was demonstrated that uPAR was upregulated in serum samples from patients with CRC and uPAR expression levels were associated with advanced stages of CRC and distant metastasis in patients. In CRC cells, uPAR was demonstrated to promote cell proliferation, migration and invasion, but inhibited cell apoptosis. Furthermore, the results demonstrated that uPAR expression was negatively regulated via miR-561-3p, via the binding of miR-561-3p to its 3’-untranslated region. Moreover, uPAR reduced the activation of the PI3K/AKT signaling pathway. In conclusion, uPAR was downregulated via miR-561-3p and potentially contributed to tumorigenesis via the PI3K/AKT signaling pathway in CRC.