Abstract
BackgroundAccumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. However, the biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear.MethodCircRNAs were verified by Sanger sequencing. Colony formation, 5-Ethynyl-2′-deoxyuridine (EdU), and Transwell assays were performed to investigate the effect of circBFAR on the proliferation, invasion, and migration of PDAC cells in vitro. RNA pull-down assays were conducted to verify the binding of circBFAR with microRNA miR-34b-5p.ResultsIn the present study, we identified a novel circRNA (termed as circBFAR, hsa_circ_0009065) that was upregulated in a 208-case cohort of patients with PDAC. The ectopic expression of circBFAR correlated positively with the tumor-node-metastasis (TNM) stage and was related to poorer prognosis of patients with PDAC. Moreover, circBFAR knockdown dramatically inhibited the proliferation and motility of PDAC cells in vitro and their tumor-promoting and metastasis properties in in vivo models. Mechanistically, circBFAR upregulated mesenchymal-epithelial transition factor (MET) expression via sponging miR-34b-5p. Additionally, circBFAR overexpression increased the expression of MET and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which ultimately promoted the progression of PDAC cells. Importantly, application of MET inhibitors could significantly attenuate circBFAR-mediated tumorigenesis in vivo.ConclusionsOur findings showed that circBFAR plays an important role in the proliferation and metastasis of PDAC, which might be explored as a potential prognostic marker and therapeutic target for PDAC.
Highlights
IntroductionAccumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression
Accumulating evidence suggests that circular RNAs are important participants in cancer progression
CircBFAR overexpression increased the expression of mesenchymalepithelial transition factor (MET) and activated downstream phosphorylation of Akt (Ser 473) and further activated the MET/PI3K/Akt signaling pathway, which promoted the progression of pancreatic ductal adenocarcinoma (PDAC) cells
Summary
Accumulating evidence suggests that circular RNAs (circRNAs) are important participants in cancer progression. The biological processes and underlying mechanisms of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. It is crucial to further explore the biological and molecular mechanism of PDAC progression and develop a molecule-oriented method for early diagnosis and targeted therapy. Some circRNAs have been found to interact with RNA binding proteins (RBPs) or function as templates for protein translation [15, 16]. Previous studies have demonstrated that circRNAs exert impact on biological processes of cancers, including proliferation, migration, invasion, and apoptosis [17]. The potential correlation between circRNAs and PDAC progression and the underlying mechanism remains unclear
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