Abstract
Objective Increased expression of KDM1A and decreased expression of DACT1 in cervical cancer cells were noticed in a previous study. This study is aimed at exploring the mechanism behind the KDM1A regulation on DACT1 in cervical cancer cells. Methods The expression profile of KDM1A and DACT1 in cervical cancer tissues was searched in TCGA database. In vitro experiments verified the effect of KDM1A and DACT1 on proliferation and migration ability of cervical cancer cell lines after cell transfection. The interaction of KDM1A with HDAC1 was identified by coimmunoprecipitation (Co-IP). The expression levels of KDM1A and DACT1 in cervical cancer cell lines were determined by qRT-PCR and western blot. Results TCGA database showed that cervical cancer tissues had elevated expression of KDM1A and decreased expression of DACT1, which was consistent with the observation in cervical cancer cell lines. KDM1A was found to negatively regulate DACT1 through histone deacetylation. Meanwhile, the downregulation of KDM1A or overexpression of DACT1 could suppress the cell proliferation and migration ability in HeLa and SiHa cells. Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression. Conclusion KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.
Highlights
As the second most common malignant cancer in female, cervical cancer is characterized by poor prognosis in the advanced stage due to metastasis or recurrence [1]
The results showed that KDM1A was highly expressed and DACT1 (305/3) was lowly expressed in cervical cancer tissues (Figures 1(a) and 1(b), p < 0:01)
Thereafter, we measured the mRNA and protein expression levels of KDM1A and DACT1 in cervical cancer cell lines (HeLa, Ca Ski, SiHa, and C-33A) and immortalized human cervical epithelial cell line H8. qRT-PCR and western blot demonstrated that compared with H8 cells, the mRNA (Figure 1(e), p < 0:01) and protein (Figure 1(f), p < 0:01)
Summary
As the second most common malignant cancer in female, cervical cancer is characterized by poor prognosis in the advanced stage due to metastasis or recurrence [1]. This disease is curable in the early stage. Early screening as an effort to enhance early detection and treatment for cervical cancer is of paramount importance [2]. Compounds with histone deacetylase (HDAC) inhibitory activity are proved to be attractive therapeutic approaches for cervical cancer considering the implication of epigenetic regulations in the tumorigenesis of this disease [6]
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