- Title
- LncRNA IDH1-AS1 links the functions of c-Myc and HIF1a via IDH1 to regulate the Warburg effect
- Creator
- Xiang, Shaoxun; Gu, Hao; Jin, Lei; Thorne, Rick F.; Zhang, Xu Dong; Wu, Mian
- Relation
- Proceedings of the National Academy of Sciences of the United States of America Vol. 115, Issue 7, p. E1465-E1474
- Publisher Link
- http://dx.doi.org/10.1073/pnas.1711257115
- Publisher
- National Academy of Sciences
- Resource Type
- journal article
- Date
- 2018
- Description
- The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1a, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two m ajor regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1a in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased a-KG and decreased ROS production and subsequent HIF1a down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1a. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.
- Subject
- c-Myc; HIF1a; IDH1-AS1; Warburg effect; IDH1; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1466413
- Identifier
- uon:47540
- Identifier
- ISSN:0027-8424
- Rights
- Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
- Language
- eng
- Full Text
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