Identification of circ_0085616 as an Upregulated and Oncogenic Circular RNA in Cervical Cancer Via the miR-503-5p-Mediated ATXN7L3 Activation.

Abstract

Background: Increasing evidence enhanced the recognition of circular RNAs (circRNAs) implicated in cancer progression. CircRNA_0085616 (circ_0085616) is a novel circRNA with high expression in cervical cancer (CC); its function and action mechanism are explored during this study.

Methods: The measurement of circ_0085616, microRNA-503-5p (miR-503-5p), and Ataxin-7L3 (ATXN7L3) was performed via quantitative real-time polymerase chain reaction. Next, 3-(4,5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and colony formation assays were implemented to analyze the proliferative ability. Cell metastasis was evaluated by using transwell migration and invasion assays. Glycolysis was analyzed by using glucose consumption, lactate and adenosine triphosphate production. Western blot was employed for protein analysis. The target binding was performed by dual-luciferase reporter assay and RNA immunoprecipitation assay. An animal experiment in vivo was conducted by xenografts.

Results: Circ_0085616 was heightened and its downregulation blocked cellular proliferation, metastasis, and glycolysis in CC. Then, we found that circ_0085616 had a sponge effect on miR-503-5p and the miR-503-5p inhibitor could ameliorate the effects of circ_0085616 knockdown on CC cells. In addition, miR-503-5p directly targeted ATXN7L3 to obstruct CC cell proliferation, metastasis, and glycolytic process. Further, circ_0085616 could enhance ATXN7L3 by sequestering miR-503-5p, and the miR-503-5p/ATXN7L3 axis was also responsible for circ_0085616 on promoting CC tumorigenesis in vivo.

Conclusion: It was obvious that circ_0085616 facilitated the carcinogenic effect on CC via the activation of ATXN7L3 by sponging miR-503-5p. Our study may be likely to provide a novel molecular target for CC therapy.