Long non‐coding RNA HOTAIR acts as a competing endogenous RNA to promote glioma progression by sponging miR‐126‐5p

• Published in: Journal of cellular physiology 2018-09, Vol.233 (9), p.6822-6831
• Main Authors: Liu, Liang, Cui, Sitong, Wan, Teng, Li, Xiaojian, Tian, Wei, Zhang, Rui, Luo, Liangsheng, Shi, Yan
• Format: Article
• Language: English
• Subjects: Antisense RNA; Bioinformatics; ceRNA; Gene expression; Glioma; GLS; Glutaminase; glutamine metabolism; HOTAIR; MiR‐126‐5p; Molecular chains; Ribonucleic acid; RNA; Transcription; Tumorigenesis
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26432

LncRNA HOX transcript antisense intergenic RNA (HOTAIR) has been shown to play prominent roles in tumorigenesis. However, its precise molecular mechanism in glioma has not been completely elucidated. In this study, we found that HOTAIR was aberrantly up‐regulated in glioma tissues and was negatively correlated with miR‐126‐5p expression. Next, we determined that HOTAIR promote glioma progression by sponging miR‐126‐5p. Subsequently, glutaminase (GLS) was confirmed to be a direct target of miR‐126‐5p using bioinformatics software and a luciferase reporter assay. Moreover, HOTAIR could modulate GLS expression by functioning as a competing endogenous RNA (ceRNA) for miR‐126‐5p. Taken together, our study clarified that the HOTAIR/miR‐126/GLS pathway is involved in glioma progression and may potentially serve as a target for glioma therapy. Our results revealed that, HOTAIR is significantly overexpressed in HGG and is associated with glioma cell glutamine metabolism, angiogenesis, and invasion. HOTAIR is associated with miR‐126‐5p, which suppresses glioma cell glutamine metabolism, angiogenesis, and invasion. MiR‐126‐5p regulates glioma glutamine metabolism, angiogenesis, and invasion by targeting GLS. HOTAIR, as a ceRNA, regulates GLS by competitively binding miR‐126‐5p. Inhibition of endogenous HOTAIR expression suppresses glioma growth in vivo. To support cell propagation, cellular metabolism is reprogrammed to balance biosynthetic processes with energy supply in cancer cells. The effects of miR‐126‐5p on glutamine catabolism, angiogenesis, invasion, and sensitivity to TMZ were largely abrogated by GLS expression. HOTAIR could modulate GLS expression by functioning as a competing endogenous RNA (ceRNA) for miR‐126‐5p.