Abstract
BackgroundCircular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.MethodscircRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.ResultsWe identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.Conclusionscirc-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.
Highlights
Circular RNAs have recently been shown to play important roles in different tumors
We further examined the results in HPDE and six Pancreatic ductal adenocarcinoma (PDAC) cell lines, and the results indicated that circ-ASH2L was barely expressed in HPDE cells, but its expression was much higher in PDAC cells (Fig. 1b)
To further probe whether circ-ASH2L was related to tumor malignancy, circ-ASH2L expression was detected in Hs 766 T, Hs 766 T-L1, Hs 766 T-L2 and Hs 766 T-L3 cells (Hs 766 T-L1, Hs 766 T-L2 and Hs 766 T-L3 cells are the first, second and third-generation primary tumor cells, respectively, with increasing invasive ability and were derived from a liver metastasis of Hs 766 T cells); as the malignancy of PDAC cells increased, the expression levels of circ-ASH2L increased successively (Fig. 1c)
Summary
Circular RNAs (circRNAs) have recently been shown to play important roles in different tumors. In recent years, increasing evidence has suggested that aberrant circRNA expression may contribute to the development of different cancers, such as lung cancer [12, 13], esophageal squamous cell carcinoma [14], hepatocellular cancer [15], colorectal cancer and so on [16, 17]. These observations indicate that circRNAs may be a new class of potential biomarkers or therapeutic targets for cancer [7]. Pancreatic cancer-related circRNAs have not been fully elucidated and should be further studied
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