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

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.