MiR-205 Inhibits Sporadic Vestibular Schwannoma Cell Proliferation by Targeting Cyclin-Dependent Kinase 14

Abstract

Background: Sporadic vestibular schwannoma (VS) is a benign primary tumor that arises from the vestibular nerve. Growing VS can negatively compress the brain stem, which can lead to death. MicroRNAs (miRNAs) can negatively regulate target genes at the post-transcriptional level and are critical in tumorigenesis. Studies have demonstrated the tumor suppressive function of microRNA-205-5p (miR-205) across many cancers, but no studies have evaluated the role of miR-205 in sporadic VS. We conducted this study to examine the role of miR-205 in sporadic VS cell proliferation.

Methods: We evaluated miR-205 expression in sporadic VS tissues and normal great auricular nerve by real-time quantitative polymerase chain reaction. Then, we transfected miR-205 mimics and control oligonucleotides into sporadic VS primary cells to examine the functional significance of miR-205 expression at a cellular level by CCK8 and colony formation and used dual-luciferase reporter assays to find the target gene of miR-205.

Results: We determined that miR-205 levels were downregulated in sporadic VS tissues in comparison to normal controls. In functional assays, miR-205 suppressed proliferation and colony formation ability of sporadic VS cells. CDK14 (cyclin-dependent kinase 14) was identified as a target gene of miR-205 by bioinformatics, and validated using dual-luciferase reporter assays. Moreover, miR-205 overexpression inhibited levels of phosphorylated PI3K and Akt.

Conclusions: These findings suggested that miR-205 suppressed sporadic VS proliferation by targeting CDK14 and may be considered as a potential drug therapy for sporadic VS treatment in the future.

Keywords: Cyclin-dependent kinase 14; MiR-205; PI3K/Akt; Sporadic vestibular schwannoma.