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

被引：12
作者：
Du, Peipei [1 ,2 ]
Zhi, Yanfang [1 ]
Wang, Ruijie [3 ]
Li, Ya [1 ]
Li, Huanhuan [1 ]
Zhang, Xiaoan [4 ]
Cheng, Guomei [3 ]
Li, Xiaofu [1 ]
机构：
[1] Zhengzhou Univ, Dept Cytopathol, Affiliated Hosp 3, 7 Front Kangfu St, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Acad Med Sci, Dept Cytopathol, Zhengzhou, Peoples R China
[3] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou, Peoples R China
[4] Zhengzhou Univ, Dept Imaging, Affiliated Hosp 3, Zhengzhou, Peoples R China
来源：
REPRODUCTIVE SCIENCES | 2021年 / 28卷 / 02期
关键词：
Long non-coding RNA; Promoter methylation; SOX21-AS1; Cervical cancer; Diagnosis; LONG NONCODING RNA; HUMAN-PAPILLOMAVIRUS; DNA METHYLATION; EPIGENETICS; PROLIFERATION; CHROMATIN; DISEASE; LNCRNA;
D O I：
10.1007/s43032-020-00335-y
中图分类号：
R71 [妇产科学];
学科分类号：
100211 ;
摘要：
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 beta-catenin/c-myc/cyclin D1 mRNA levels (r(s) = - 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.
引用
收藏
页码：532 / 540
页数：9
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