Long Noncoding RNA linc00665 Stabilized by TAF15 Impeded the Malignant Biological Behaviors of Glioma Cells via STAU1 Mediated mRNA Degradation

Abstract

BACKGROUND: Glioma is a poor prognostic brain cancer with strong invasiveness and limited treatment options. Moreover, lncRNAs dysregulation has emerged as important component in tumorigenesis, and participated in diverse biomolecular regulatory networks of glioma therapies. METHODS: RNA FISH assays and lncRNA microarrays were used to determine the expression of linc00665. RNA-IP, RNA pull-down, ChIP and luciferase reporter gene assays were used to testify the association among TAF15/linc00665/MTF1(YY2)/GTSE1 axis in glioma. RESULTS: In this study, we demonstrated that TAF15 and linc00665 were identified as tumor-suppressors in glioma. Moreover, TAF15 overexpression enhanced the stability of linc00665 and inhibited malignant progression of glioma cells. Both MTF1 and YY2 showed high expression level, while knockdown of either MTF1 or YY2 inhibited malignant progression of glioma. Mechanistically, overexpression of linc00665 was cofirmed to destabilize MTF1 and YY2 mRNAs respectively by interacting with STAU1. Moreover, knockdown of MTF1 or YY2 decreased the expression levels of GTSE1 through direct binding to GTSE1 promoter region. CONCLUSIONS: Our study aimed to clarify important roles of TAF15/linc00665/MTF1(YY2)/GTSE1 axis in modulating malignant progression of glioma cells, and might propose novel mechanisms in which lncRNA functions via affecting STAU1-mediated mRNA stability in glioma, thus contribute to molecular therapies for glioma. FUNDING STATEMENT: This work is supported by grants from the Nature Science Foundation of China (81573010, 81672511 and 81502179), Liaoning Science and Technology Plan Project (No. 2017225020, 2015225007), Project of Key Laboratory of Neuro-oncology in Liaoning Province (112-2400017005), special developmental project guided by central government of Liaoning Province (No. 2017011553-301). DECLARATION OF INTERESTS: The authors declare no competing interests. ETHICS APPROVAL STATEMENT: Normal brain tissues and four grade of human brain tissues obtained from patients who have signed the Informed consent hospitalized in the Department of Neurosurgery of Shengjing Hospital of China Medical University, moreover our study was approved by the Ethics Committee of Shengjing Hospital of China Medical University. All assays on nude mice were operated strictly according to the protocol approved by the Administrative Panel on Laboratory Animal Care of the Shengjing Hospital.