Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis.
Circular RNA CircEYA3 induces energy production to promote pancreatic ductal adenocarcinoma progression through the miR-1294/c-Myc axis.
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环状RNA CircEYA3通过miR-1294/c-Myc轴诱导能量产生促进胰腺导管腺癌进展
DOI：
10.1186/s12943-021-01400-z
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发表时间：
2021-08-21
期刊：
影响因子：
37.3
通讯作者：
Liang C
中科院分区：
文献类型：
--
作者：
Rong Z;Shi S;Tan Z;Xu J;Meng Q;Hua J;Liu J;Zhang B;Wang W;Yu X;Liang C
研究背景大量研究表明，环状RNA（circular RNA，circRNA）在人类多种肿瘤的发生、发展中起着关键作用。方法利用基因表达数据集（GEO）分析CircEYA 3基因在胰腺导管腺癌（PDAC）中的表达情况，并对该基因在PDAC中的表达及调控作用进行研究。应用qRT-PCR检测PDAC细胞和组织中circRNA、miRNA和mRNA的表达。通过进行一系列功能实验来确定circEYA 3在体外和体内的生物学作用。进一步采用双荧光素酶报告基因、荧光原位杂交（FISH）、RNA pull-down分析和RNA免疫沉淀（RIP）分析等方法证实circEYA 3与miR-1294的相互作用。结果circEYA 3在PDAC组织和细胞中表达升高，circEYA 3表达水平越高，PDAC患者预后越差。在功能上，circEYA 3通过ATP合成增加能量产生，以促进体外和体内PDAC进展。结论CircEYA 3通过miR-1294/c-Myc信号通路促进PDAC的发生发展，CircEYA 3可能是PDAC有效的分子治疗靶点。
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.
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