Oncotarget

Research Papers:

Zinc finger protein 91 (ZFP91) activates HIF-1α via NF-κB/p65 to promote proliferation and tumorigenesis of colon cancer

Juan Ma, Chunliu Mi, Ke Si Wang, Jung Joon Lee and Xuejun Jin _

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Oncotarget. 2016; 7:36551-36562. https://doi.org/10.18632/oncotarget.9070

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Abstract

Juan Ma1, Chunliu Mi1, Ke Si Wang1, Jung Joon Lee1, Xuejun Jin1

1Key Laboratory of Natural Resources of Changbai Mountain & Functional Molecules, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China

Correspondence to:

Xuejun Jin, e-mail: [email protected]

Keywords: ZFP91, HIF-1α, NF-κ B/p65, tumorigenesis, colon cancer

Received: October 11, 2015    Accepted: April 16, 2016    Published: April 28, 2016

ABSTRACT

Zinc finger protein 91 (ZFP91) has been reported to be involved in various biological processes. However, the clinical significance and biological role of ZFP91 in colon cancer remains unknown. Here, we show that ZFP91 expression is upregulated in patients with colon cancer. We found that ZFP91 upregulated HIF-1α at the levels of promoter and protein in colon cancer cells. Using chromatin immunoprecipitation, electrophoretic mobility shift assay and luciferase reporter gene assay, we found that NF-κB/p65 is required for the binding of ZFP91 to the HIF-1α promoter at -197/-188 base pairs and for the transcriptional activation of HIF-1α gene mediated by ZFP91. Flow cytometry, 5-ethynyl-2′-deoxyuridine (EdU) incorporation and tumor xenograft assay demonstrated that ZFP91 enhanced cell proliferation of colon cancer through upregulating HIF-1α in vitro and in vivo. Furthermore, ZFP91 is positively associated with HIF-1α in human colon cancer. Thus, we concluded that ZFP91 activates transcriptional coregulatory protein HIF-1α through transcription factor NF-κB/p65 in the promotion of proliferation and tumorigenesis in colon cancer cell. ZFP91 may serve as a driver gene to activate HIF-1α transcription in the development of cancer.


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PII: 9070