Abstract

BackgroundCircular RNAs (circRNAs) is a novel class of non-coding RNAs that regulate gene expression during cancer progression. Circ_0092314 is a newly discovered circRNA that was upregulated in pancreatic cancer (PAAD) tissues. However, the detailed functions and underlying mechanisms of circ_0092314 in PAAD cells remain unclear.MethodsWe first determined the expression of circ_0092314 in PAAD and normal tissues and further investigated the functional roles of circ_0092314 in regulating epithelial-mesenchymal transition (EMT) of PAAD cells. We also assessed the regulatory action of circ_0092314 on the microRNA-671 (miR-671) and its target S100P.ResultsCirc_0092314 was markedly upregulated in PAAD tissues and cells, and its overexpression was closely correlated with worse prognosis of PAAD patients. Functionally, circ_0092314 promotes proliferation, invasion and EMT in vitro and tumor growth in vivo. Mechanistically, we demonstrated that circ_0092314 directly binds to miR-671 and relieve its suppression of the downstream target S100P, which induces EMT and activates the AKT signaling pathway. The tumor-promoting effects caused by overexpression of circ_0092314 could be revered by re-expression of miR-671 in PAAD cells.ConclusionsOverall, our study demonstrates that circ_0092314 exerts critical roles in promoting the EMT features of PAAD cells, and provides insight into how elevated expression of circ_0092314 might influence PAAD progression.

Highlights

  • Circular RNAs is a novel class of non-coding RNAs that regulate gene expression during cancer progression

  • To investigate the biological role of circ_0092314 in Pancreatic ductal adenocarcinoma (PAAD), we first analyzed its expression in 40 pairs of PAAD specimens and adjacent normal tissues using Quantitative Real-Time PCR (qRT-PCR) assay

  • We further examined the contribution of S100P in miR-671dependent Epithelial-mesenchymal transition (EMT) by performing rescue experiments

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Summary

Introduction

Circular RNAs (circRNAs) is a novel class of non-coding RNAs that regulate gene expression during cancer progression. Circ_0092314 is a newly discovered circRNA that was upregulated in pancreatic cancer (PAAD) tissues. The detailed functions and underlying mechanisms of circ_0092314 in PAAD cells remain unclear. Pancreatic ductal adenocarcinoma (PAAD) is a highly aggressive cancer type, being characterized by high rates of metastasis and resistance to chemotherapy [1]. Epithelial-mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose contact between neighboring cells and acquire migratory mesenchymal phenotypes [2]. The pancreatic cancer stem cells express cell surface markers, such as CD44 and CD133 [3]. It is considered that cancer cells can enter the CSC state via activation of the EMT program [4]

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