2. Academic Validation
  3. CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α

CIRBP is a novel oncogene in human bladder cancer inducing expression of HIF-1α

  • Cell Death Dis. 2018 Oct 12;9(10):1046. doi: 10.1038/s41419-018-1109-5.
Mengxin Lu 1,  Qiangqiang Ge 1,  Gang Wang 2 3 4,  Yongwen Luo 1,  Xiaolong Wang 5,  Wei Jiang 2 3 6,  Xuefeng Liu 7,  Chin-Lee Wu 8,  Yu Xiao 1 2 3 4,  Xinghuan Wang 9 10
Affiliations

Affiliations

  • 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 3 Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
  • 4 Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 5 Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany.
  • 6 Medical Research Institute, Wuhan University, Wuhan, China.
  • 7 Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, DC, USA.
  • 8 Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 9 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. wangxinghuan@whu.edu.cn.
  • 10 Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China. wangxinghuan@whu.edu.cn.
PMID: 30315244 DOI: 10.1038/s41419-018-1109-5
Abstract

Cold-inducible RNA binding protein (CIRBP) has been reported to be associated with distinct tumorigenesis. In this study, we investigated the role of CIRBP in human bladder Cancer (BCa), indicating that CIRBP is overexpressed in BCa tissues and cell lines to promote proliferation and migration. Moreover, CIRBP could induce expression of HIF-1α via binding to the 3'-UTR of its mRNA to increase the mRNA stability in BCa cells. Furthermore, we demonstrated that PTGIS is a HIF-1α targeted gene, a major regulator in hypoxic Cancer progression by activating transcription of various oncogenes. Our results also suggested that overexpression of HIF-1α may suppress the expression of PTGIS in BCa cells, by binding to HRE sequence at the promoter region of PTGIS. In addition, we found a strongly downregulation of PTGIS in BCa tissue and transcriptionally inhibited by HIF-1α in BCa cells, which could be triggered by its DNA methylation. Further result suggested that knockdown of CIRBP could promote the expression of PTGIS, meanwhile knockdown of PTGIS could partially rescue CIRBP-deficiency induced inhibition of migration and proliferation in BCa cells. Taken together, our study indicated that CIRBP could be a novel oncogene in human bladder Cancer inducing transcription of HIF-1α, which could inhibit expression of methylated PTGIS.

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