Abstract
BackgroundCircular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. However, the expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC).MethodsqRT-PCR analysis was performed to detect the expression of circATXN7, miR-4319 and ENTPD4 in GC tissues and cells. CCK-8, colony formation, EdU, flow cytometry, TUNEL and transwell assays were conducted to assess the effect of circATXN7 or miR-4319 on cell proliferation, apoptosis and invasion. In vivo assays were utilized to further analyze the function of circATXN7 on the tumorigenesis and progression of GC. The interaction between miR-4319 and circATXN7 (or ENTPD4) was verified using luciferase reporter and RNA pull-down assays.ResultsThe results showed an upregulated circATXN7 expression in GC tissues and cell lines. Besides, silenced circATXN7 hampered the proliferation and invasion as well as promoted the apoptosis in GC cells. Moreover, low expression of miR-4319 was found in GC. It was determined that circATXN7 acted as a sponge for miR-4319 and had a negative association with miR-4319. We also found that miR-4319 upregulation restrained GC cell proliferation and migration whereas enhanced apoptosis. Subsequently, ENTPD4, the target gene of miR-4319, was found overexpressed in GC. Additionally, it was negatively correlated with miR-4319 whereas positively associated with circATXN7. In vivo experiments, circATXN7 silence was confirmed to inhibit GC tumor growth.ConclusionsCircATXN7 promoted GC development through sponging miR-4319 and regulating ENTPD4, which identified circATXN7 as a new biomarker in GC.
Highlights
Circular RNAs which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process
CircATXN7 stability was analyzed after MGC-803 and AGS cells were treated with Actinomycin D
ectonucleoside triphosphate diphosphohydrolase 4 (ENTPD4) was confirmed as a target gene of miR‐4319 To further support competing endogenous RNA (ceRNA) hypothesis, here, we explored the target gene of miR-4319
Summary
Circular RNAs (circRNAs) which are shown as a class of RNAs exhibit the importance in the regulation of gene expression and the development of biological process. The expression profile and molecular mechanism of circRNA ATXN7 (circATXN7) is still mostly uncertain in gastric cancer (GC). Zhang et al Cancer Cell Int (2020) 20:25 loop feature, and the sponge effect of circRNAs was more potent than that of linear RNAs [4]. CircRNAs were hypothesized to be the competing endogenous RNA (ceRNA), competitively combining with miRNAs and regulating mRNAs, including GC [9]. CircLARP4 was reported to inhibit GC cell proliferation and invasion by regulating miR-424-5p/LATS1 axis [12]. Exploring the biological function and molecular mechanism of circATXN7 in GC is of great meaning for developing a novel biomarker for GC treatment
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