Abstract
The abnormal expression of microRNAs (miRNAs or miRs) with oncogenic or tumor‑suppressive roles in pancreatic ductal adenocarcinoma (PDAC) has been widely reported in recent years, and these dysregulated miRNAs are implicated in the formation and progression of PDAC. Therefore, an investigation into the functional roles of miRNAs in PDAC may facilitate the identification of effective therapeutic targets. miRNA‑664 (miR‑664) has been found to be aberrantly expressed and to play crucial roles in several human cancer types. However, the expression pattern and functional roles of miR‑664 in the malignant capacity of PDAC have yet to be elucidated. In this study, the results revealed that miR‑664 was clearly downregulated in PDAC tissues and cell lines. The low miR‑664 expression was strongly associated with pathological T stage and lymph node metastasis of the patients with PDAC. Patients with PDAC with a low miR‑664 expression had a poorer overall survival and a worse disease‑free survival than those patients with a high miR‑664 level. Functional experiments suggested that exogenous miR‑664 expression suppressed the growth and metastasis of PDAC cells in vitro, whereas miR‑664 downregulation exerted the opposite effects. In addition, miR‑664 suppressed the tumor growth of PDAC cells in vivo. Mechanistically, paired box protein 6 (PAX6) was identified as a direct target gene of miR‑664 in PDAC cells. Furthermore, PAX6 was upregulated in PDAC tissues, and its upregulation inversely correlated with miR‑664 levels. Moreover, the silencing of PAX6 mimicked the effects of miR‑664 upregulation in PDAC cells, and the recovered expression of PAX6 eliminated the effects of miR‑664 on PDAC cells. Notably, miR‑664 could inhibit the activation of PI3K/Akt pathway in PDAC cells in vitro and in vivo. Cumulatively, these results indicate an important role of the miR‑664/PAX6 pathway in suppressing the aggressiveness of PDAC cells, suggesting that miR‑664 may be an attractive therapeutic target for the treatment of patients with this fatal disease.