HBXIP activates the PPAR?/NF-?B feedback loop resulting in cell proliferation.

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 PPAR? (peroxisome proliferator-activated receptor-?) 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 PPAR? and that HBXIP activated the transcription activity of PPAR? in an NF-?B (p65)-dependent manner. Moreover, Co-immunoprecipitation and immunofluorescence analysis showed that HBXIP bound to NF-?B/p65 in the cells. Interestingly, we found that PPAR? could conversely increase the expression of NF-?B/p65 through activating its transcription activity. In addition, the clinical observations showed that both HBXIP and PPAR? were highly expressed in colonic carcinoma, and HBXIP expression was positively associated with that of PPAR? 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-?B/PPAR?, which promoted the fast proliferation of the colonic cancer cells. Therapeutically, HBXIP may serve as a potential drug target of colonic cancer cells.

SUBMITTER: Liu Q 

PROVIDER: S-EPMC5787476 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature