Research Paper Volume 11, Issue 5 pp 1427—1439
FoxD2-AS1 promotes glioma progression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway
- 1 Department of Neurosurgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunan Province, China
- 2 Department of Neurosurgery, Yunnan Cancer Hospital, Kunming 650118, Yunan Province, China
- 3 Department of Neurosurgery, Yunnan Cancer Center, Kunming 650118, Yunan Province, China
- 4 Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunan Province, China
- 5 Department of Radiation Oncology, Yunnan Cancer Hospital, Kunming 650118, Yunan Province, China
- 6 Department of Radiation Oncology, Yunnan Cancer Center, Kunming 650118, Yunan Province, China
- 7 Equal contribution
Received: September 21, 2018 Accepted: February 21, 2019 Published: March 11, 2019
https://doi.org/10.18632/aging.101843How to Cite
Abstract
Background/Aims: The present study was aimed at exploring the role of long noncoding RNA (lncRNA) FOXD2-AS1 in the development and progression of glioma and the underlying mechanism of FOXD2-AS1/miR-185-5p/HMGA2 network in glioma via regulation of PI3K/Akt signaling pathway.Methods: Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. qRT-PCR and Western blot were used to determine the expression of FOXD2-AS1. The potential effects of FOXD2-AS1 on the viability, mobility and apoptosis of glioma cells were evaluated using MTT assay, Transwell assays and flow cytometry. The xenograft tumor model was performed to examine the influence of the lncRNA FOXD2-AS1/miR-185-5p/HMGA2 network on the biological functions of glioma cells. Luciferase assay and immunoprecipitation assay were examined to dissect molecular mechanisms.
Results: LncRNA FOXD2-AS1 was overexpressed in human glioma, and upregulated FOXD2-AS11 expression indicated higher WHO grade (p < 0.05). MiR-185-5p was downregulated, whereas HMGA2 was upregulated in glioma tissues in comparison with para-carcinoma tissues. FOXD2-AS1 could regulate the expression of HMGA2 via miR-185-5p. Knockdown of FOXD2-AS1 significantly inhibited proliferation and metastatic potential of glioma cells, whereas endogenous expression FOXD2-AS1 inhibited the glioma cell activity through targeting HMGA2.
Conclusions: lncRNA FOXD2-AS1 acted as a sponge of miR-185-5p and influenced the PI3K/Akt signaling pathway through regulating HMGA2. LncRNA FOXD2-AS1 modulated HMGA2 and PI3K/Akt downstream signaling through sponging miR-185-5p, thereby promoting tumorigenesis and progression of glioma.