eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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SCImago Journal & Country Rank
5/2019
vol. 15
 
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abstract:
Basic research

Proteinase-activated receptor-2 enhances Bcl2-like protein-12 expression in lung cancer cells to suppress p53 expression

Guoyuan Ma
,
Chao Wang
,
Baoyu Lv
,
Yuanzhu Jiang
,
Lei Wang

Arch Med Sci 2019; 15 (5): 1147–1153
Online publish date: 2019/08/02
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Introduction
The pathogenesis of lung cancer is unclear. Less expression of p53 or p53 mutation was identified in lung cancer cells, which plays a role in the development of lung cancer. Recent reports indicate that Bcl2-like protein-12 (Bcl2L12) can inhibit the expression of p53. Lung cancer cells express proteinase-activated receptor-2 (PAR2). This study tests the hypothesis that activation of PAR2 inhibits the expression of p53 in lung cancer cells.

Material and methods
Lung cancer cells were collected from patients with non-small cell lung cancer (NSCLC). The cells were exposed to active peptides or trypsin in the culture for 48 h. The expression of p53 was assessed by RT-qPCR and Western blotting.

Results
We observed that lung cancer cells express Bcl2L12. Activation of PAR2 increases expression of Bcl2L12 in lung cancer cells. Bcl2L12 mediates PAR2-suppressed p53 expression in lung cancer cells. IgE-activated mast cell suppression of p53 expression in lung cancer cells can be prevented by knocking down Bcl2L12. The Bcl2L12 bound Mdm2, the transcription factor of p53, to prevent the Mdm2 from binding to the promoter of p53 and thus inhibited p53 expression in lung cancer cells. PAR2 could attenuate lung cancer cell apoptosis via inducing Bcl2L12.

Conclusions
Lung cancer cells express Bcl2L12, which mediates the effects of activation of PAR2 on suppressing the expression of p53 in lung cancer cells, implying that Bcl2L12 may be a novel therapeutic target for the treatment of lung cancer.

keywords:

lung cancer, proteinase-activated receptor-2, Bcl2-like protein-12, mast cells, immunoglobulin E

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