LncRNA APTR amplification serves as a potential glioma biomarker and promotes glioma progression via miR-6734-5p/ TCF7/LEF1 axis

Abstract

Background

Alu-mediated p21 transcriptional regulator (APTR) overexpression is detected in different human cancers; however, few reports have investigated APTR gene amplification conditions. Furthermore, whether APTR amplification is related to glioma malignancy and the underlying mechanism remain unknown.

Methods

APTR amplification and expression levels in 153 glioma samples were analyzed using qPCR. Correlations between APTR and patient prognosis were evaluated using Kaplan-Meier survival and COX regression analyses. Both in vitro and in vivo phenotypic assays were performed to confirm the carcinogenic effects of APTR in glioblastoma (GBM) cells. RNA-sequencing and RNA immunoprecipitation and luciferase reporter assays were performed to confirm APTR as a competing endogenous RNA (ceRNA) and to identify the downstream axis of APTR.

Results

Our results suggest that APTR amplification and overexpression are novel independent diagnostic biomarkers for predicting poor prognosis in patients with gliomas. APTR knockdown significantly repressed the proliferation and invasion of GBM cells, both in vitro and in vivo. APTR was demonstrated to absorb miR-6734-5p and upregulate TCF7 and LEF1 expression. Taken together, these results suggest that APTR promotes the malignant phenotypes of GBM by inducing TCF7 and LEF1 expression.

Conclusion

We identified APTR as a novel prognostic biomarker in patients with gliomas and confirmed that APTR is a ceRNA that promotes glioma progression via the APTR/miR-6734-5p/TCF7/LEF1 axis.