Circ_0019435 Exerts Its Functions in the Cellular Process of Cervical Cancer via Epigenetically Silencing DKK1 and PTEN.

Cervical cancer (CC) is the most serious gynecological malignancy among women worldwide. As a subtype of noncoding RNAs (ncRNAs), circular RNAs (circRNAs) play important roles in the regulation of gene expression and cancer progression. It was discovered from the cancer-specific circRNA database (CSCD) that circ_0019435 was mainly distributed in the nucleus of HeLa-S3 cells. However, few researches have mentioned circ_0019435 with its function in cancers. The present study uncovered that circ_0019435 was upregulated in CC cells by qRT-PCR. Moreover, circ_0019435 was more stable than its linear isoform-ABCC2. Besides, no regulation of circ_0019435 on ABCC2 and the chemoresistance of CC cells were found. Then, it was unveiled by a series of functional assays including colony formation, trypan blue staining, and transwell invasion assays in that circ_0019435 ablation induced the suppression of proliferation, invasion, and EMT of HeLa and SiHa cells. The subcellular distribution of circ_0019435 was assessed by subcellular fractionation and FISH assay. Furthermore, it was disclosed that circ_0019435 binds to EZH2 to silence DKK1 and PTEN. Finally, rescue assays corroborated that DKK1 and PTEN were involved in circ_0019435-mediated CC cell progression. In conclusion, circ_0019435 regulates DKK1 and PTEN expression at the epigenetic level, thereby influencing the progression of CC cells.