Silencing of circular RNA_0000326 inhibits cervical cancer cell proliferation, migration and invasion by boosting microRNA-338-3p-dependent down-regulation of CDK4

Abstract

Cervical cancer is one of the leading causes of cancer-related death among women, which is attributed partly by limited treatment options. Recent studies have provided in-depth explanations regarding the role of circular RNA in cancers. We aimed to investigate the role of circular RNA_0000326 in cervical cancer. Bioinformatics analysis revealed a high circ_0000326 expression in cervical cancer. Cervical cancer cells and tissues were also observed to have elevated levels of circ_0000326 and the upregulation of circ_0000326 depended on the stage of cancer. Transfection with siRNA of circ_0000326 resulted in the inhibition of proliferation, migration and cell cycle of cancer cells. Interestingly, we confirmed that circ_0000326 served as a sponge for microRNA-338-3p and that the miRNA bound to Cyclin-dependent kinase 4. In the presence of microRNA-338-3p mimic or silencing of circ_0000326, Cyclin-dependent kinase 4 expression was decreased. Transfection with microRNA-338-3p mimic inhibited cell clone formation and proliferation. Moreover, in vivo experiment revealed that the injection of shRNA-circ_0000326 lentivirus suppressed tumor growth and decreased Cyclin-dependent kinase 4 expression. Taken altogether, our results showed that circ_0000326 exerted oncogenic effects on cervical cancer by upregulating Cyclin-dependent kinase 4 via sponging microRNA-338-3p. This systematic investigation on circ_0000326 could provide further insight into cervical cancer.