Circ_0044362 Facilitates the Progression of Epithelial Ovarian Cancer via Enhancing HOXB4 Transcription to Activate the RUNX1/IGFBP3 Axis.

Abstract

Increasing numbers of studies have elucidated the emerging roles of circular RNA (circRNA) in cancer progression. However, the function of circRNAs in modulating their parental genes in ovarian cancer remains poorly understood. In this study, we identified that circ_0044362, a circRNA derived from homeobox B4 (HOXB4), significantly promotes the expression of its parental gene HOXB4 in ovarian cancer. Functionally, circ_0044362 promotes the malignant phenotypes of ovarian cancer cells. Further analysis revealed that circ_0044362 facilitates the transcriptional activation of its parental gene HOXB4 by directly guiding U1 small nuclear ribonucleoprotein (snRNP) to its promoter region, thereby enhancing the oncogenic behaviors of ovarian cancer cells. Furthermore, HOXB4 positively regulates runt-related transcription factor 1 (RUNX1) expression, with RUNX1 serving as a transcription factor to promote the transcription of insulin-like growth factor binding protein-3 (IGFBP3). Notably, inhibitors of either HOXB4, RUNX1, or IGFBP3 could reverse the oncogenic activity mediated by circ_0044362. Collectively, our findings reveal the involvement of the circ_0044362/HOXB4 pathway in ovarian cancer progression and provide potential therapeutic strategies for ovarian cancer treatment.