Oncotarget

Research Papers:

HBXIP activates the PPARδ/NF-κB feedback loop resulting in cell proliferation

Qian Liu, Wenbin Lu, Chunxia Yang, Yue Wang, Wenjing Li, Ying Chu, Jianzhong Deng, Yongzhong Hou and Jianhua Jin _

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Oncotarget. 2018; 9:404-417. https://doi.org/10.18632/oncotarget.23057

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Abstract

Qian Liu1,*, Wenbin Lu1,*, Chunxia Yang1, Yue Wang1, Wenjing Li1, Ying Chu1, Jianzhong Deng1, Yongzhong Hou2 and Jianhua Jin1

1Department of Oncology, The Changzhou Wujin People’s Hospital, Jiangsu Province, 213017, China

2Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu Province, 212013, China

*These authors contributed equally to this work

Correspondence to:

Jianhua Jin, email: [email protected]

Yongzhong Hou, email: [email protected]

Keywords: HBXIP; PPARδ; NF-κB; proliferation; colonic cancer

Received: July 10, 2017     Accepted: November 14, 2017     Published: December 08, 2017

ABSTRACT

Hepatitis B X-interacting protein (HBXIP, also termed as LAMTOR5) plays a crucial role in regulation of cancer progression, while the mechanism is still unclear. Here we found that HBXIP increased the expression of PPARδ (peroxisome proliferator-activated receptor-δ) in gene and protein levels of SW480 or HT-29 colonic cancer cells. Chromatin immunoprecipitation and luciferase reporter assays showed that HBXIP occupied the core promoter (−1079/−239 nt) regions of PPARδ and that HBXIP activated the transcription activity of PPARδ in an NF-κB (p65)-dependent manner. Moreover, Co-immunoprecipitation and immunofluorescence analysis showed that HBXIP bound to NF-κB/p65 in the cells. Interestingly, we found that PPARδ could conversely increase the expression of NF-κB/p65 through activating its transcription activity. In addition, the clinical observations showed that both HBXIP and PPARδ were highly expressed in colonic carcinoma, and HBXIP expression was positively associated with that of PPARδ in the clinical specimen. Importantly, HBXIP expression levels were positively correlated with the clinical pathological parameters including lymph node metastasis and advanced TNM stage. These findings suggest that HBXIP served as a co-activator to activate the positive feedback regulations of NF-κB/PPARδ, which promoted the fast proliferation of the colonic cancer cells. Therapeutically, HBXIP may serve as a potential drug target of colonic cancer cells.


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