Circ_0072995 drives cervical cancer development by regulating the miR-29a/WDR5 axis

Abstract

Circular RNA_0072995 (Circ_0072995) is involved in the pathogenesis of cancers; however, no study has investigated its role in cervical cancer. Therefore, we aimed to investigate the function of circ_0072995 in cervical cancer. Normal human cervical epithelial cells (hCECs), HeLa cells, and forty female nude BALB/c mice were used. Immunohistochemistry, invasion assays, flow cytometric analysis, luciferase assays, and tumour volume measurements were performed to explore the potential mechanism. Circ_0072995 was significantly up-regulated in cancer tissues, and its level was markedly correlated with the International Federation of Gynecology and Obstetrics system (FIGO) staging. In vitro studies revealed that circ_0072995 interacts with miR-29a to induce WD repeat domain 5 (WDR5) expression and promotes the proliferation and invasion of cells, but inhibits apoptosis of cells. Knockdown of circ_0072995 or WDR5, or overexpression of miR-29a significantly inhibited tumour growth in vivo. In conclusion, circ_0072995 promoted cervical cancer development by inducing miR-29a-mediated WDR5 expression. Impact statement What is already known on this subject? Global Cancer Statistics 2020 estimated that there were 1 021,494 new cases of cervical cancer and 439 201 deaths from cervical cancer. Circ_0072995 was first shown to promote breast cancer development in 2018. Subsequent studies have revealed that circ_0072995 is also involved in the development of other cancers, including epithelial ovarian cancer and hepatocellular carcinoma. However, no studies have explored the association between circ_0072995 and cervical cancer. What do the results of this study add? We hypothesized that circ_0072995 drives cervical cancer development by sponging miRNAs and inducing the expression of key factors involved in tumorigenesis. Based on this hypothesis, we investigated the role of circ_0072995 in cervical cancer and paracancerous tissues and explored the underlying mechanism in both in vitro and in vivo studies. What are the implications of these findings for clinical practice and/or further research? For the first time, our study revealed the key role of WDR5 in cervical cancer progression regulated by circ_0072995. We first reported the promoting effects of circ_0072995 in cervical cancer development by inducing miR-29a mediated WDR5 expression and also revealed the therapeutic potential of circ_0072995, miR-29a, and WDR5 in cervical cancer.