Long intergenic non-protein coding RNA 00475 silencing acts as a tumor suppressor in glioma under hypoxic condition by impairing microRNA-449b-5p-dependent AGAP2 up-regulation

Lei Yu; Si Gui; Yawei Liu; Xiaoyu Qiu; Binghui Qiu; Xi'an Zhang; Jun Pan; Jun Fan; Songtao Qi; Guozhong Zhang

doi:10.1177/1758835920940936

Long intergenic non-protein coding RNA 00475 silencing acts as a tumor suppressor in glioma under hypoxic condition by impairing microRNA-449b-5p-dependent AGAP2 up-regulation

Ther Adv Med Oncol. 2020 Aug 11:12:1758835920940936. doi: 10.1177/1758835920940936. eCollection 2020.

Authors

Lei Yu¹, Si Gui², Yawei Liu³, Xiaoyu Qiu³, Binghui Qiu³, Xi'an Zhang³, Jun Pan³, Jun Fan³, Songtao Qi³, Guozhong Zhang¹

Affiliations

¹ Department of Neurosurgery, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Guangzhou 510515, Guangdong Province, P. R. China.
² Department of Radiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, P. R. China.
³ Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.

Abstract

Objective: Long non-coding RNAs have been demonstrated to be involved in the progression of a variety of cancers, including glioma. Through microarray analyses, long intergenic non-protein coding RNA 00475 (LINC00475) was identified in the glioma development. However, its potential role remains incompletely understood. This study aimed to elucidate the effect of LINC00475 on the development of glioma under hypoxic conditions.

Methods: Glioma cells underwent hypoxic treatment and were collected. The functional role of LINC00475 and AGAP2 in glioma was determined using ectopic expression, depletion, and reporter assay experiments. Then, the expression of LINC00475, microRNA (miR)-449b-5p, AGAP2, FAK, and HIF-1α was determined. In addition, cell migration and invasion were examined. Finally, a tumor xenograft was carried out in nude mice to explore the role of LINC00475 on oxidation in vivo.

Results: LINC00475 was identified to be overexpressed in hypoxic glioma samples, which was further observed to bind to and down-regulate miR-449b-5p, and negatively targeted AGAP2. Moreover, we also revealed a positive correlation between LINC00475 and AGAP2 expression in glioma. In addition, silencing of LINC00475 decreased the extent of FAK phosphorylation and reduced the expression of HIF-1α and AGAP2. It was also observed that LINC00475 silencing suppressed glioma cell proliferation, migration, and invasion, and promoted cell apoptosis. Moreover, oxidation of nude mice was promoted by LINC00475 silencing.

Conclusion: Taken together, LINC00475 silencing exerted an inhibitory effect on glioma under hypoxic conditions by down-regulating AGAP2 via up-regulation of miR-449b-5p.

Keywords: AGAP2; LINC00475; glioma; hypoxia; invasion; miR-449b-5p; migration.