A HOTAIR regulatory element modulates glioma cell sensitivity to temozolomide through long-range regulation of multiple target genes
- Lei Zhang1,5,
- Anshun He1,5,
- Bohan Chen1,
- Jinfang Bi1,
- Jun Chen1,
- Dianhao Guo1,
- Yuyang Qian1,
- Wenbin Wang1,
- Tengfei Shi1,
- Zhongfang Zhao1,
- Jiandang Shi1,
- Woojin An2,3,
- Frank Attenello3,4 and
- Wange Lu1
- 1State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, 300071, Tianjin, China;
- 2Department of Biochemistry and Molecular Medicine, Norris Cancer Center, University of Southern California, Los Angeles, California 90033, USA;
- 3Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA;
- 4Department of Neurological Surgery, University of Southern California, Los Angeles, California 90033, USA
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↵5 These authors contributed equally to this work.
Abstract
Temozolomide (TMZ) is a frequently used chemotherapy for glioma; however, chemoresistance is a major problem limiting its effectiveness. Thus, knowledge of mechanisms underlying this outcome could improve patient prognosis. Here, we report that deletion of a regulatory element in the HOTAIR locus increases glioma cell sensitivity to TMZ and alters transcription of multiple genes. Analysis of a combination of RNA-seq, Capture Hi-C, and patient survival data suggests that CALCOCO1 and ZC3H10 are target genes repressed by the HOTAIR regulatory element and that both function in regulating glioma cell sensitivity to TMZ. Rescue experiments and 3C data confirmed this hypothesis. We propose a new regulatory mechanism governing glioma cell TMZ sensitivity.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.251058.119.
- Received March 30, 2019.
- Accepted January 8, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
