Previous studies have shown that miR-222-3p is a tumor-suppressive miRNA in ovarian cancer (OC). Here, researchers aimed to further understand the regulatory role of miR-222-3p in ovarian cancer and provide new mechanisms for its prevention and treatment. The researchers found that miR-222-3p inhibits the migration and proliferation of ovarian cancer cells. CDK19 is highly expressed in ovarian cancer and is negatively correlated with miR-222-3p. Furthermore, miR-222-3p directly binds to the 3′-UTR of CDK19 and inhibits its translation, thereby inhibiting the migration and proliferation of ovarian cancer cells in vitro and inhibiting tumor growth in vivo. They also observed that Hotair inhibits miR-222-3p in ovarian cancer. In addition, Hotair can promote the proliferation and migration of ovarian cancer cells in vitro and promote tumor growth and metastasis in vivo. Moreover, the expression of Hotair is positively correlated with the expression of CDK19. These results indicate that Hotair indirectly upregulates the expression of CDK19 by "sponging" miR-222-3p, thereby enhancing the malignant behavior of ovarian cancer.
Here, researchers investigated the function of CDK19. Both colony formation assays (Figure 1I) and EdU assays showed a significant increase in cell proliferation in CDK19 overexpressing OVCAR3 cells. To determine whether miR-222-3p inhibits ovarian cancer cell proliferation by targeting CDK19, the researchers designed the following rescue experiment. In both colony formation assays and EdU assays, overexpression of CDK19 abolished the inhibitory effect of miR-222-3p mimics on OVCAR3 cell proliferation (Figure 1J, K). As expected, colony formation assays and flow cytometry experiments showed that overexpression of CDK19 could also abolish the inhibitory effect of miR-222-3p mimics on HO-8910 PM cell proliferation. Furthermore, compared to the control group, the group co-transfected with miR-ctrl mimics and CDK19 showed higher levels of CDK19 mRNA and protein. Similarly, the CDK19 mRNA and protein levels, which were suppressed by miR-222-3p mimics, were effectively restored in CDK19-overexpressing HO-8910 PM cells.
Figure 1. miR-222-3p inhibits ovarian cancer cell proliferation by targeting CDK19. (Fan L, et al., 2022)