MiR-20a Promotes Prostate Cancer Cell Proliferation By Targeting NR4A3 / 中国生物化学与分子生物学报

ABSTRACT

Prostate cancer is a common malignant tumor in male patients. It is of great clinical significance to explore the pathogenesis of prostate cancer and find suitable therapeutic targets. NR4A3 is derived from the nuclear hormone receptor superfamily of steroids, and NR4A3 plays an important role in the malignant progression of a variety of tumors. However, its role in prostate cancer has not yet been elucidated. Therefore, this project intends to investigate the role of NR4A3 in prostate cancer and screen for miRNAs that target NR4A3, which may help find potential target for the diagnosis and treatment of prostate cancer. The GEPIA website predicts that NR4A3 is under-expressed in prostate cancer tissues, and qRT-PCR data confirmed downregulation of NR4A3 in prostate cancer cells (P<0. 01). CCK8 and clone formation experiments show that overexpression of NR4A3 can significantly inhibit the viability, the number and size of colonies of prostate cancer cells (P < 0. 01). The bioinformatics website predicts that NR4A3 may be the target gene of miR-20a, and qRT-PCR showed that miR-20a expression was elevated in prostate cancer cells (P<0. 01). Furthermore, dual luciferase reporter gene experiment confirmed that miR-20a can target two sites of 3′-UTR of NR4A3 (P<0. 05, P<0. 001). Western blot results showed that miR-20a can inhibit the expression of NR4A3. CCK8 experiments further found that miR-20a inhibitor can significantly reduce the viability of prostate cancer cells(P<0. 05), while miR-20a mimic has the opposite effect (P<0. 05, P<0. 01). CCK8 and clone formation experiments showed that when co-transfected with miR-20a mimic and pcDNA3. 1-NR4A3 recombinant plasmids, up-regulation of NR4A3 could partially offset the viability, the number and size of colonies of PC3 cells promoted by miR-20a mimic (P <0. 05). In summary, miR-20a promotes the proliferation of prostate cancer cells by targeting NR4A3.