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Aberrant Methylation of the SOX21-AS1 Promoter Region Promotes Gene Expression and Its Clinical Value in Cervical Cancer

Reproductive Sciences volume 28, pages 532–540 (2021)Cite this article

Abstract

Cervical cancer is the fourth most common female cancer worldwide. Long non-coding RNAs (lncRNAs), such as SOX21-AS1, play pivotal roles in the progression and metastasis of cancer. We previously described that SOX21-AS1 was hypomethylated in cervical cancer (CC) and aimed to further explore the relationship between methylation of the SOX21-AS1 promoter and CC using clinical cervical samples. Pyrosequencing was performed to detect the methylation status of the SOX21-AS1 promoter in 33 cervical specimens. Additionally, expression levels of related genes in 43 clinical cervical specimens were measured using quantitative real-time PCR (qRT-PCR). The SOX21-AS1 promoter was significantly hypomethylated in CC (P < 0.01). SOX21-AS1 hypomethylation was also significantly associated with an advanced Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.01). The expression levels of SOX21-AS1 and SOX21 were noted to be higher in cancer vs. normal cervix (all P < 0.001). Moreover, the expression of SOX21-AS1 was positively correlated with SOX21 in all samples (r = 0.891, P < 0.001). Methylation statue of the SOX21-AS1 promoter region was negatively correlated with the expression levels of SOX21-AS1 and SOX21 (SOX21-AS1, r = − 0.628; SOX21, r = − 0.648; both P < 0.001). The methylation status of SOX21-AS1 displayed promising diagnostic potential for CC, exhibiting good sensitivity (100.0%) and specificity (69.2%), with an area under the curve of 0.846. In addition, bioinformatic analyses identified a potential link between SOX21-AS1 and the Wnt signaling pathway. Furthermore, methylation status of SOX21-AS1 was negatively correlated with β-catenin/c-myc/cyclin D1 mRNA levels (rs = − 0.529, − 0.462 ,and − 0.383, respectively, P < 0.05). Our findings illuminated that lncRNA SOX21-AS1 showed hypomethylation in cervical cancer and SOX21-AS1 could serve as a novel biomarker for CC diagnosis or a potential therapeutic target.

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Acknowledgments

We would like to thank Linlin Zhang, Yaming Liu, and Haiyang Yu for the prominent technical assistance and valuable suggestions.

Funding

This study was supported by the Science and Technology Department of Henan, China (Grant Number: 22170005) and Science and Technology Department of Henan, China (Grant Number: LHGJ20190392).

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Affiliations

  1. Department of Cytopathology, The Third Affiliated Hospital of Zhengzhou University, No. 7 Front Kangfu Street, Er’qi District, Zhengzhou, 450052, China

    Peipei Du, Yanfang Zhi, Ya Li, Huanhuan Li & Xiaofu Li

  2. Department of Cytopathology, Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China

    Peipei Du

  3. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Ruijie Wang & Guomei Cheng

  4. Department of Imaging, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Xiaoan Zhang

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  1. Peipei Du
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  2. Yanfang Zhi
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  3. Ruijie Wang
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  4. Ya Li
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Correspondence to Xiaofu Li.

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All the research has been approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University.

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Peipei Du and Yanfang Zhi are joint first authors.

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Du, P., Zhi, Y., Wang, R. et al. Aberrant Methylation of the SOX21-AS1 Promoter Region Promotes Gene Expression and Its Clinical Value in Cervical Cancer. Reprod. Sci. 28, 532–540 (2021). https://doi.org/10.1007/s43032-020-00335-y

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  • DOI: https://doi.org/10.1007/s43032-020-00335-y

Keywords

  • Long non-coding RNA
  • Promoter methylation
  • SOX21-AS1
  • Cervical cancer
  • Diagnosis