Abstract
BackgroundEpiplakin1 (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. However, the role of Eppk1 in cervical cancer (CC) remains unknown.MethodsTo express Eppk1 and KLF5 and their correlation, we used RNA-sequence, RT-qPCR, TCGA database and immunofluorescence staining in vitro and in different pathological cervical tissues. In CC cell lines, we tested adenovirus-mediated over expression or knockdown of KLF5 and siRNA-mediated knockdown of Eppk1 and a suiting assessment of cell proliferation and cell signaling by western blot and CCK8 tests. We studied the mechanism by which KLF5 regulates Eppk1 expression by reporter gene test and chromatin immunoprecipitation test.ResultsEppk1 expression promoted in CC tissues and cell lines compared with increased KLF5 expression. The results of immunofluorescence staining further showed the increased co-expression of Eppk1 and KLF5 correlated substantially with tumorigenesis in cervical tissues. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanically, KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments reported that KLF5 promoted cell proliferation in Hela partly dependent on Eppk1 upregulation. Besides, KLF5-mediated activation of p38 signaling significantly decreased after Eppk1 knockdown compared with decline of proliferation, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation. Finally, Eppk1 expression is positively correlated with tumor size in clinicopathological features of CC.ConclusionsEppk1 may be an effective therapeutic target for affecting p38 signaling pathway and cell proliferation in cervical cancer.
Highlights
Cervical cancer (CC) is globally the most common malignancy of the female reproductive and usually affects young women [1]
Our previous study found that Kruppel-like factors 5 (KLF5) plays a role in cytoskeleton aggregation and proliferation, and plays an important role in the growth of CC [12], suggesting that there may be a link between Eppk1 and KLF5 expression taking part in CC development
Eppk1 expression significantly increases in CC tissues and cell lines To examined whether levels of Eppk1 would alter in cervical cancer, we performed RNA expression profiling using RNA-sequence analyses of human CC tissues (n = 3) and normal cervical tissues (n = 3)
Summary
Cervical cancer (CC) is globally the most common malignancy of the female reproductive and usually affects young women [1]. Plakin protein binds cytoskeleton myofilaments and anchors at the cytoplasmic membrane junction. It is a part of EGF signaling and works in cytoskeleton aggregation and proliferation signal transduction of tumor cells [6]. Our previous study found that KLF5 plays a role in cytoskeleton aggregation and proliferation, and plays an important role in the growth of CC [12], suggesting that there may be a link between Eppk and KLF5 expression taking part in CC development. Epiplakin (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. The role of Eppk in cervical cancer (CC) remains unknown
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