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Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical cancer
Author(s) -
Chen Yurou,
Liu Fulin,
Wu Kejia,
Wu Wanrong,
Wu Hanshu,
Zhang Wei
Publication year - 2018
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3056
Subject(s) - biology , cyclin d1 , apoptosis , cell growth , cancer research , transfection , cancer cell , hela , mmp2 , cell cycle , microbiology and biotechnology , cell culture , cancer , metastasis , biochemistry , genetics
Background DPP8 is a member of the dipeptidyl peptidase IV family, which belongs to the S9b protease subfamily. It regulates cell proliferation, apoptosis, migration and invasion during cancer progression. Methods To investigate the role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer tissues and cells. The localization of DPP8 was determined by immunofluorescence staining. Subsequently, SiHa and HeLa cells were treated with small interfering RNA (siRNA)‐DPP8. We used cell cycle analysis, an 5‐ethyl‐2′‐deoxyuridine assay proliferation assay and a cellular apoptosis assay to determine the effect of DPP8 on the proliferation and apoptosis of cervical cancer cells. We used a Transwell assay to assess the number of transfection cancer cells migrating through the matrix. A real‐time polymerase chain reaction and western blot analysis were used to analyze the expression of related proteins and to determine the phenotype caused by the depletion or overexpression of DPP8 in cervical cancer cells. Results We observed that DPP8 was highly expressed in cervical cancer tissues and cells. DPP8 expression was observed in the cytosol and in the perinuclear area, as well as in the nuclei of cervical cancer cells. Notably, when cells were treated with siRNA‐DPP8, the expression of BAX increased, and the expression of cyclin D1, Bcl‐2, MMP2 and MMP9 was downregulated. In cervical cancer cell lines, silencing the expression of DPP8 not only suppressed the proliferation, migration and invasion of the cervical cancer cells, but also promoted cervical cancer cell apoptosis. Conclusions The data obtained in the present study reveal that DPP8 promotes the progression of cervical cancer.