A HIF1A/miR-485-5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia.

Abstract

The high aggressiveness of gliomas remains a huge challenge to clinical therapies, and the hypoxic microenvironment in the core region is a critical contributor to glioma aggressiveness. In this study, it was found that miR-485-5p was low expressed within glioma tissue samples and cells. GO enrichment annotation indicated that the predicted downstream targets miR-485-5p were enriched in hypoxia response and decreased oxygen level. In glioma cells, miR-485-5p overexpression suppressed cell viability, migratory ability, and invasive ability under both normoxic and hypoxic conditions. Through direct binding, miR-485-5p suppressed SRPK1 expression. Under hypoxia, SRPK1 overexpression enhanced hypoxia-induced glioma cell aggressiveness and significantly reversed the effects of miR-485-5p overexpression. Moreover, HIF1A could target the miR-485-5p promoter region to inhibit the transcription. HIF1A, miR-485-5p, and SRPK1 form a regulatory axis, which modulates glioma cell aggressiveness under hypoxia. In conclusion, we identify a HIF1A/miR-485-5p/SRPK1 axis that modulates the aggressiveness of glioma cells under hypoxia. The axis could potentially provide new research avenues in the treatment of gliomas considering the hypoxic environment in its core.

• Authors: Lei Cheng, Renjun Peng, Pin Guo, Hongliang Zhang, Dingyang Liu, Xinbin Liao, Yi Liu, Xin Mo, Yiwei Liao
• Journal: Experimental cell research (Exp Cell Res) Vol. 402 Issue 1 Pg. 112547 (05 01 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 33722639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• MIRN485 microRNA, human
• MicroRNAs
• SRPK1 protein, human
• Protein Serine-Threonine Kinases

Topics

• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Glioma (genetics, pathology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics)
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology)
• Neoplasm Staging
• Protein Serine-Threonine Kinases (genetics)
• Signal Transduction (genetics)
• Tumor Hypoxia (genetics)
• Tumor Microenvironment (genetics)