Promoter hypermethylation of SOX11 promotes the progression of cervical cancer in vitro and in vivo

Li,Xiaofang; Wu,Xiaoling; Li,Yun; Cui,Yumeng; Tian,Run; Singh,Namita; Ding,Muyang; Yang,Yang; Gao,Yan'e

doi:10.3892/or.2019.6993

Promoter hypermethylation of SOX11 promotes the progression of cervical cancer in vitro and in vivo

Authors:
- Xiaofang Li
- Xiaoling Wu
- Yun Li
- Yumeng Cui
- Run Tian
- Namita Singh
- Muyang Ding
- Yang Yang
- Yan'e Gao
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Affiliations: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Obstetrics and Gynecology, The Affiliated Cixi Hospital, Wenzhou Medicine University, Cixi, Zhejiang 325000, P.R. China , Department of Orthopedics, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, P.R. China
Published online on: February 1, 2019 https://doi.org/10.3892/or.2019.6993
Pages: 2351-2360

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Abstract

The development of cervical cancer (CC) is a multi‑gene, multi‑step carcinogenic process that involves complex genetic and epigenetic mechanisms. SRY‑related HMG‑box gene 11 (SOX11) is a member of the SOX family of transcription factors with an emerging crucial role in the development of various tumor types. To elucidate the function of SOX11 in cervical carcinogenesis, the expression level of SOX11 during the development of human CC was analyzed by immunohistochemistry and western blot analysis. Additionally, the methylation status of the SOX11 was examined using bisulfite sequencing and methylation‑specific polymerase chain reaction. The SOX11 expression and promoter methylation in human CC cell lines were also determined. The effect of SOX11 expression restoration after 5‑aza‑2'‑deoxycytidine (5‑Aza‑dC) treatment on the CC cell proliferation ability was evaluated in CC cell lines. SOX11 was highly expressed in normal cervix (NC) and precancerous low‑grade squamous intraepithelial lesions, but weakly expressed or virtually absent in precancerous high‑grade squamous intraepithelial lesions and CC, which is consistent with the result of the western blot analysis. Hypermethylation of the SOX11 promoter was detected in CC, which was significantly higher than that in NC samples at each CpG site. The expression level of SOX11 in the CC cell lines was downregulated compared with the positive control, Tera‑1human teratoma cell line. Upon 5‑Aza‑dC treatment, SOX11 expression was significantly upregulated in the CC cell lines at the mRNA and protein levels, and cell proliferation was inhibited. The results indicated that the downregulation of SOX11 in CC is due to the hypermethylation of the SOX11 promoter region. Thus, SOX11 methylation may have a role in the growth of CC cells and cervical carcinogenesis.

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