Abstract

BackgroundCircular RNAs (circRNAs) are implicated in the carcinogenesis of human cancers. However, the functional roles of circRFX3 in glioma are not elucidated.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) assay was performed for the levels of circRFX3, RFX3, miR-1179, miR-1229 and vasodilator stimulated phosphoprotein (VASP). Actinomycin D assay and RNase R assay were employed to analyze the characteristics of circRFX3. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted for cell proliferation. Transwell assay was used for cell migration and invasion. Flow cytometry analysis was adopted for cell apoptosis. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to analyze the interaction between miR-1179/miR-1229 and circRFX3 or VASP. Western blot assay was conducted for VASP protein level. Murine xenograft model assay was used to investigate the role of circRFX3 in vivo.ResultsCircRFX3 level was increased in glioma tissues and cells. Knockdown of circRFX3 suppressed glioma cell proliferation, migration and invasion and promoted apoptosis in vitro and repressed tumorigenesis of glioma in vivo. MiR-1179 and miR-1229 were identified to be the targets of circRFX3. MiR-1179 or miR-1229 inhibition reversed the impacts of circRFX3 knockdown on glioma cell malignant behaviors. Additionally, VASP was demonstrated to be the target gene of miR-1179 and miR-1229, and VASP overexpression abolished the effect of circRFX3 knockdown on glioma cell progression.ConclusionCircRFX3 served as a tumor promoter in glioma via modulating miR-1179/miR-1229-VASP axis, which might provide a novel target for glioma therapy.

Highlights

  • Glioma is a common central nervous system cancer, ranking the ­6th cause in cancer-associated deaths worldwide [1, 2]

  • CircRFX3 level was elevated in glioma tissues and cell lines To clarify the functions of circRFX3 in glioma progression, the expression level of circRFX3 in glioma tissues and normal tissues was firstly determined by Quantitative real-time polymerase chain reaction (qRT-PCR) assay

  • These results indicated that circRFX3 might be a prognostic marker for glioma

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Summary

Introduction

Glioma is a common central nervous system cancer, ranking the ­6th cause in cancer-associated deaths worldwide [1, 2]. The main treatment strategies for glioma contain surgery, radiotherapy and chemotherapy [3]. The prognosis of patients with high-grade glioma is still far from satisfactory [4]. People have gradually realized that the occurrence and development of glioma are extremely complex processes [2]. Circular RNAs (circRNAs) are a family of singlestranded closed non-coding RNAs (ncRNAs) with neither 5’-terminal nor 3’-terminal poly A tails [6, 7]. CircRNAs can regulate gene abundance through functioning. Circular RNAs (circRNAs) are implicated in the carcinogenesis of human cancers. The functional roles of circRFX3 in glioma are not elucidated

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