Abstract
BackgroundmiR-26a plays a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. However, the function of miR-26a in pancreatic cancer has not been clearly elucidated. The present study was designed to determine the roles of miR-26a in pancreatic cancer and its association with the survival of patients with pancreatic cancer.MethodsThe expression of miR-26a was examined in 15 pairs of pancreatic duct adenocarcinoma (PDAC) and their adjacent benign pancreatic tissues (ABPT), by qRT-PCR. The results were confirmed by in situ hybridization using two panels of 106 PDACs and their ABPT microarray. The association of miR-26a expression with overall survival was determined. The proliferation and cell cycle distribution of Capan-2, SW-1990, and Panc-1 cells, transfected with miR-26a mimics or a miR-26a inhibitor, were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. The cell tumorigenicity was evaluated via murine xenograft experiments. Cyclin D2, E2, EZH2, and PCNA levels were analyzed by Western blot and immunohistochemistry.ResultsmiR-26a was expressed in the cytoplasm of pancreatic ductal epithelial cells, whereas its expression was significantly downregulated in PDAC tissues compared with that of ABPT. Patients with low miR-26a expression had a significantly shorter survival than those with high miR-26a expression. The in vitro and in vivo assays showed that overexpression of miR-26a resulted in cell cycle arrest, inhibited cell proliferation, and decreased tumor growth, which was associated with cyclin E2 downregulation.ConclusionsmiR-26a is an important suppressor of pancreatic ductal carcinoma, and can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.
Highlights
Pancreatic cancer, pancreatic duct adenocarcinoma (PDAC), is the fourth most common cause of cancer-related deaths worldwide
The majority of these patients were in Stage II (70.8%), indicating that the findings are important to patients who are still surgically resectable with the best chance for a 5-year survival. Quantitative RealTime PCR (qRT-PCR) analysis demonstrated that miR-26a expression was significantly lower in PDAC tissues than in normal tissues (n = 15, P,0.05; Fig. 1A), which was further confirmed by the Locked nucleic acid (LNA)-in situ hybridization (ISH) analysis of 106 cases of PDAC
LNA-ISH showed that miR-26a was present in the cytoplasm of pancreatic ductal epithelial cells (Figs. 1C and 1D)
Summary
Pancreatic cancer, pancreatic duct adenocarcinoma (PDAC), is the fourth most common cause of cancer-related deaths worldwide. MiRNAs are naturally occurring, small, single-stranded, noncoding RNAs that mediate gene expression at the post-transcriptional and translational levels in both plants and animals [5,6]. These molecules play critical roles in human cancers such as pancreatic cancer [7,8], as well as in cancer behavior, including its proliferation, invasion, migration, apoptosis, and drug resistance. The miRNA functional network of cancer is related to several aspects of tumor pathogenesis [9] This network may be used to assess the diagnosis and prognosis of cancer as well as to evaluate possible therapeutic options. The present study was designed to determine the roles of miR-26a in pancreatic cancer and its association with the survival of patients with pancreatic cancer
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