Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis

Zeyin Rong,Qingcai Meng,Chen Liang,Jie Hua,Jin Xu,Jiang Liu,Wei Wang,Xianjun Yu,Zhen Tan,Bo Zhang,Si Shi

doi:10.1186/s12943-021-01400-z

Abstract

BackgroundExtensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. However, the expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear.MethodsCircEYA3 was explored based on Gene Expression Omnibus (GEO) dataset analysis. qRT-PCR was applied to determine the expression of circRNAs, miRNAs and mRNAs in PDAC cells and tissues. The biological roles of circEYA3 in vitro and in vivo were determined by performing a series of functional experiments. Further, dual luciferase reporter, fluorescence in situ hybridization (FISH), RNA pull-down assays, and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of circEYA3 with miR-1294.ResultsCircEYA3 was elevated in PDAC tissues and cells, and a higher level of circEYA3 was significantly associated with a poorer prognosis in patients with PDAC. Functionally, circEYA3 increased energy production via ATP synthesis to promote PDAC progression in vitro and in vivo. Mechanistically, circEYA3 functions as an endogenous miR-1294 sponge to elevate c-Myc expression, thus exerting its oncogenic functions.ConclusionCircEYA3 promotes the progression of PDAC through the miR-1294/c-Myc signalling axis, and circEYA3 may be an efficient molecular therapeutic target in PDAC.

Highlights

Extensive studies have demonstrated the pivotal roles of circular RNAs in the occurrence and development of different human cancers
Discovery of oncogenic circRNAs and characterization of circEYA3 in pancreatic ductal adenocarcinoma (PDAC) To search for potential circRNAs involved in PDAC progression, we systematically analysed the differentially expressed circRNAs in PDAC tissues compared with adjacent noncancerous tissues in two open-access published Gene Expression Omnibus (GEO) datasets (GSE79634 and GSE69362) [23, 24]
The results of quantitative real-time PCR (qRT-PCR) and GEO dataset analysis showed that the level of hsa_circ_0007895 was prominently increased in PDAC tissues compared with adjacent normal tissues, and hsa_circ_0007895 was selected for further study (Fig. S1A and S1B)

Summary

Introduction

Extensive studies have demonstrated the pivotal roles of circular RNAs (circRNAs) in the occurrence and development of different human cancers. The expression and regulatory roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) are unclear. Accumulating studies have shown that circRNAs are abnormally aberrantly expressed and participate in the pathogenesis of different cancers, such as lung cancer [8], gastric cancer [9], colorectal cancer [10], osteosarcoma [11], and melanoma [12]. In PDAC, some dysregulated circRNAs have been identified to play crucial roles in proliferation and progression. To the best of our knowledge, some dysregulated circRNAs have been reported to play crucial roles in the initiation and development of PDAC [15], here are still many unknowns that need exploration and study to elucidate the underlying mechanisms of circRNAs in PDAC

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Discussion

Conclusion