SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line.

Danijela Stanisavljevic,Marija Gredic,Isidora Petrovic,Marija Schwirtlich,Vladanka Vukovic,Jelena Popovic,Milena Stevanovic,Sumitra Deb

doi:10.1371/journal.pone.0184686

Danijela Stanisavljevic, Marija Gredic + Show 6 more

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https://doi.org/10.1371/journal.pone.0184686

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Abstract

SOX14 is a member of the SOX family of transcription factors mainly involved in the regulation of neural development. Recently, it became evident that SOX14 is one of four hypermethylated genes in cervical carcinoma, considered as a tumor suppressor candidate in this type of malignancy. In this paper we elucidated the role of SOX14 in the regulation of malignant properties of cervical carcinoma cells in vitro. Functional analysis performed in HeLa cells revealed that SOX14 overexpression decreased viability and promoted apoptosis through altering the expression of apoptosis related genes. Our results demonstrated that overexpression of SOX14 initiated accumulation of p53, demonstrating potential cross-talk between SOX14 and the p53 signaling pathway. Further analysis unambiguously showed that SOX14 triggered posttranslational modification of p53 protein, as detected by the significantly increased level of phospho-p53 (Ser-15) in SOX14-overexpressing HeLa cells. Moreover, the obtained results revealed that SOX14 activated p53 protein, which was confirmed by elevated p21Waf1/Cip1, a well known target gene of p53. This study advances our understanding about the role of SOX14 and might explain the molecular mechanism by which this transcription factor could exert tumor suppressor properties in cervical carcinoma.

Highlights

SOX family of genes encode for transcription factors that are conserved across species and participate in important developmental processes [1,2,3]
DNA extracted from HeLa and NT2/D1 cells was subjected to bisulfite conversion followed by methylation-specific PCR (MSP) reactions
For NT2/D1 cells we obtained PCR products with primer sets corresponding to both methylated and unmethylated CpG island 1, while for CpG island 3 only an unmethylated product was detected (Fig 1C). These results demonstrated that SOX14 promoter is methylated in the cervical cancer cell line, in regions encompassed by CpG islands 1 and 3, while in the embryonal carcinoma NT2/D1 cell line the SOX14 promoter has a lower methylation rate

Summary

Introduction

SOX family of genes encode for transcription factors that are conserved across species and participate in important developmental processes [1,2,3]. Members of this group of genes are involved in malignant phenotypes through their ability to regulate numerous cancer hallmarks, including cell proliferation, apoptosis, survival, invasion, migration, stemness, differentiation, senescence and angiogenesis [4]. Almost all members of the SOX family have. SOX14 activates the p53 signaling and induces apoptosis in a cervical carcinoma cell line

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