FOXA1 co-activates circODC1 and ODC1 in HPV-positive cervical cancer cell growth

Abstract

As demonstrated in previous research, hsa_circ_0052602 (circODC1) is dynamically expressed in HPV-positive cervical cancer (CC). CircODC1 expression was quantified using qRT-PCR, and its role in CC cell growth was assessed via loss-of-function assays. Interactions between miR-607 and circODC1 or ODC1 were confirmed using bioinformatics and mechanistic assays. The association of FOXA1 with the circODC1 promoter was validated through ChIP and luciferase reporter assays. CircODC1 was highly expressed in HPV-positive CC cell lines, and its depletion significantly impeded malignant processes such as proliferation, migration, and invasion. We found that ODC1 also played an oncogenic role in HPV-positive CC cells. CircODC1 was shown to positively regulate ODC1 as a ceRNA, competitively binding to miR-607 to counteract its suppression of ODC1. HPV-associated FOXA1 was identified as a potential transcription factor of circODC1. Restoration experiments showed that overexpression of circODC1 could counterbalance the inhibitory effect of FOXA1 knockdown. These findings offer new insights into therapeutic strategies for HPV-positive CC patients.

Graphical Abstract

Transcription factor FOXA1 binds to circODC1 promoter and activates circODC1 transcription. Activated circODC1 up-regulates ODC1 expression by sponging miR-607, thereby promoting HPV-positive CC cell invasion, proliferation and migration, while inhibiting apoptosis. Therefore, FOXA1 promotes HPV-positive CC progression by co-activating circODC1 and ODC1.

Keywords:

• circODC1
• miR-607
• ODC1
• FOXA1
• HPV-positive cervical cancer

Acknowledgments

We appreciate all the participants who provide supports for the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Designed the study: RJ and HFL Wrote the study: RJ Performed the experiments and prepared all the figures: SSN and HJW.

Data availability statement

Contact the corresponding author.

Additional information

Funding

This study was supported by Tianjin Binhai New District Commission of Health and Family Planning Scientific Research Project under grant (2018BWKY011) by Rong Jin; the Key Research and Development Plan of Gansu Province under grant (17YF1FA141) by Hongfang Li.