Abstract
BackgroundCircular RNA (circRNA) plays an essential role in tumor progression, including glioma. circ_0030018 is a newly discovered circRNA that is highly expressed in glioma. However, its role and mechanism in glioma need to be further elucidated.MethodsThe expression of circ_0030018, microRNA (miR)-194-5p, and tripartite motif containing 44 (TRIM44) was examined using quantitative real-time PCR. Cell proliferation, migration, invasion, and apoptosis were determined using MTT assay, colony formation assay, transwell assay, and flow cytometry. Moreover, dual-luciferase reporter assay and RNA pull-down assay were used to verify the interactions among circ_0030018, miR-194-5p, and TRIM44. The protein expression of TRIM44 was assessed by western blot analysis. Animal experiments were conducted to explore the role of circ_0030018 in glioma tumor growth in vivo.Resultscirc_0030018 was overexpressed in glioma tissues and cells, and its silencing could inhibit glioma cell proliferation, migration, invasion, and accelerate apoptosis. miR-194-5p could be sponged by circ_0030018, and its overexpression could hinder the progression of glioma cells. Further experiments revealed that miR-194-5p inhibitor reversed the negative regulation of circ_0030018 knockdown on glioma cell progression. In addition, TRIM44 was a target of miR-194-5p, and its downregulation could repress glioma cell progression. Overexpressed TRIM44 reversed the inhibition effect of miR-194-5p on glioma cell progression. Animal experiments suggested that circ_0030018 knockdown could reduce glioma tumor growth through regulating miR-194-5p and TRIM44.ConclusionOur 8data showed that circ_0030018 enhanced glioma progression by sponging miR-194-5p to regulate TRIM44, indicating that circ_0030018 might be a potential treatment target for glioma.
Highlights
Glioma is the common primary central nervous system malignant tumor in the skull, which is formed by the abnormal proliferation of glial cells [1,2]
3.8 Overexpressed tripartite motif containing 44 (TRIM44) reversed the regulation of miR-194-5p on glioma progression In LN229 and U251 cells transfected with si-circ_0030018 and in-miR-194-5p, we found that circ_0030018 silencing
We detected a significant increase in the expression of miR-194-5p and a significant decrease in the protein expression of TRIM44 in tumor tissues of sh-circ_0030018 group (Figure 9e and f)
Summary
Glioma is the common primary central nervous system malignant tumor in the skull, which is formed by the abnormal proliferation of glial cells [1,2]. In recent years, targeted therapy has been proposed to improve the survival of patients with glioma [5,6]. CircRNA has strong stability due to its special circular structure, so it has great application prospects as a therapeutic target for diseases [9,10]. In a variety of tumor types, circRNA has been discovered to be abnormally expressed and is associated with the biological behaviors of tumor cells, including glioma [11,12]. Yang et al proposed that the high circ_0030018 expression could enhance glioma cell growth and metastasis [14]. The current research on circ_0030018 in glioma is still in the preliminary stage, and more studies are needed to confirm whether it can be used as a therapeutic target for glioma
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