Long noncoding FOXD2-AS1 is activated by CREB1 and promotes cell proliferation and metastasis in glioma by sponging miR-185 through targeting AKT1.

Long non-coding RNA FOXD2-AS1 (FOXD2-AS1) has been reported to be involved in several tumors as a potential oncogene. However, its expression pattern and biological function in glioma have not been investigated. In this study, we found that FOXD2-AS1 expression was significantly up-regulated in both glioma tissues and cell lines. Additionally, CREB1 could bind directly to the FOXD2-AS1 promoter region and activate its transcription. High FOXD2-AS1 expression was significantly correlated with advanced WHO grade, KPS score and the shorter survival time of glioma patients. Next, luciferase reporter indicated that CREB1 could bind directly to FOXD2-AS1 promoter region and activate its transcription. Functional investigations revealed that knockdown of FOXD2-AS1 significantly suppressed glioma cells proliferation, migration, invasion and EMT, and promoted apoptosis. Mechanistically, our results showed that FOXD2-AS1 may act as an endogenous sponge by competing for miR-185, thereby regulating the targets of this miRNA. Taken together, our data firstly demonstrated that CREB1-induced FOXD2-AS1 contributed to glioma progression by upregulating AKT1 via competitively binding to miR-185, providing a novel strategy for targeting FOXD2-AS1 as a potential biomarker and a therapeutic target in glioma patients.