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

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 statementWhat 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.