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

Biochem Biophys Res Commun. 2019 Jan 22;508(4):1074-1081. doi: 10.1016/j.bbrc.2018.12.050. Epub 2018 Dec 13.

Abstract

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.

Keywords: CREB1; FOXD2-AS1; Glioma; LncRNA; Metastasis; miR-185.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Base Sequence
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Glioma / genetics*
  • Glioma / pathology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation / genetics

Substances

  • Cyclic AMP Response Element-Binding Protein
  • MIRN185 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA FOXD2-AS1, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt