Research Article: FoxD2-AS1 promotes glioma progression by regulating miR-185-5P/HMGA2 axis and PI3K/AKT signaling pathway

Date Published: March 15, 2019

Publisher: Impact Journals

Author(s): Wei Ni, Yaoxiong Xia, Yuxu Bi, Fan Wen, Dong Hu, Lin Luo.

http://doi.org/10.18632/aging.101843

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.

Partial Text

Glioma is one of the most common and invasive carcinomas in the central nervous system [1,2]. According to the WHO classification criterion, gliomas can be classified as grade I-IV based upon the pathological characteristics of malignant tumors. In spite of recent progress in cancer treatment, clinical prognosis and survival rate of glioma patients are still extremely low [3,4]. The malignant growth and high invasiveness of glioma cells severely constrain the therapeutic effect and cause a high recurrence rate [5]. Therefore, a better understanding of the key molecular mechanisms that mediate the development and progression of glioma will contribute to exploring novel and effective interventions.

Previous results have demonstrated that the pathogenesis of glioma requires the changes in multiple genetic pathways, and each primary and secondary glioma possesses a unique combination of these genetic changes [18]. Primary glioma is constantly characterized with loss of heterozygosity at 10q (LOH, 70%), EGFR amplification (36%), deletion ofp16INK4a (31%) and mutation of PTEN (25%) [17]. In our study, we focused on lncRNA FOXD2-AS1, which has been found to be aberrantly expressed in various cancers. In this experiment, lncRNA FOXD2-AS1 was highly expressed in human glioma tissues and cell lines. Next, we investigated the downstream molecular mechanism of FOXD2-AS1 in glioma. In this study, we found a regulatory relationship between lncRNA FOXD2-AS1 and miR-185-5p, and between miR-185-5p and HMGA2. Compared with adjacent normal tissues, the expression of miR-185-5p was down-regulated, whereas the expression of HMGA2 was up-regulated in glioma tissues. In addition, HMGA2 overexpression had the potential to promote the proliferation and migration of glioma cells, whereas miR-185-5p mimics inhibited the biological function of glioma cells by targeting HMGA2. Finally, lncRNA FOXD2-AS1 was proven to act as the sponge of miR-185-5p and affects the PI3K/AKT signal transduction pathway via regulating HMGA2.

Taken together, lncRNA FOXD2-AS1 and HMGA2 are overexpressed in glioma tissues and cell lines. A regulatory relationship exists between miR-185-5p and lncRNA FOXD2-AS1 or HMGA2. Moreover, lncRNA FOXD2-AS1 acts as a sponge of miR-185-5p to regulate HMGA2 expression and PI3K/AKT signaling pathway and subsequently promote the occurrence and progression of glioma. The findings in this study not only contribute to in-depth exploration of the exact mechanism of lncRNA FOXD2-AS1, but also provide a promising therapeutic target for the treatment of glioma.

 

Source:

http://doi.org/10.18632/aging.101843

 

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