RAD21 inhibited transcription of tumor suppressor MIR4697HG and led to glioma tumorigenesis

Background: Studies have revealed the aberrant expression of lncRNAs is responsible for human carcinogenesis. MIR4697 host gene (MIR4697HG) is an upregulated lncRNA that promoted cell growth and metastasis in other cancers. In this study, we tested the expression of MIR4697HG in glioma cells and detected the comparatively down-regulated expression. RAD1 is an upstream regulator for MIR4697HG. This study aimed at exploring the regulatory mechanism and function of RAD1/MIR4697HG/PRR12 axis in glioma. Methods: We profiled the expression of MIR4697HG in glioblastoma multiforme (GBM) tissues according to GEPIA database as well as in glioma cells by qPCR. Functional experiments confirmed relevant role of MIR4697HG in regulating glioma cell proliferation and migration. We also carried out luciferase reporter assay, pull down assay and RIP assay to verify the location and interaction among the indicated RNA molecules. Results: The expression of MIR4697HG is down-regulated significantly in glioma cells due to the up-regulated expression of RAD21. MiR-766-5p was identified functioning as a sponge for MIR4697HG and is sequestered by MIR4697HG. We also found either miR-766-5p inhibitor or PRR12 knockdown rescued the function depletion caused by MIR4697HG overexpression. In all, the down-regulated expression of MIR4697HG inhibited PRR12 to suppress glioma and led to the deterioration of glioma. Conclusion: RAD21-induced down-regulated expression of MIR4697HG is correlated with aggravation of glioma. The MIR4697HG/miR-766-5p/PRR12 axis predicts poor results in glioma and MIR4697HG could be considered as a promising biomarker for diagnosis and treatment of glioma.