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

  • Gynecologic Oncology: Original Article
  • Published:
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Abstract

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.

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Acknowledgements

We appreciate all the participants who provide supports for this research.

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Funding

This study was supported by Ningbo Natural Science Foundation (Grant No. 2019A610305) and Medical Scientific Research Foundation of Zhejiang Province (Grant No. 2020KY832).

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Authors and Affiliations

  1. Department of Gynecology, Ningbo Women & Children’s Hospital, Ningbo, 315012, Zhejiang, China

    Qiming Wang

  2. Department of Gynecology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, 315010, Zhejiang, China

    Zhihong Zhuo, Huimin Yu, Chuhan Wang & Li Gao

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  1. Qiming Wang
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  2. Zhihong Zhuo
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Correspondence to Zhihong Zhuo.

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Wang, Q., Zhuo, Z., Yu, H. et al. Circ_0019435 Exerts Its Functions in the Cellular Process of Cervical Cancer via Epigenetically Silencing DKK1 and PTEN. Reprod. Sci. 28, 2989–2999 (2021). https://doi.org/10.1007/s43032-021-00625-z

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