OncoTargets and Therapy (Jun 2020)
MicroRNA-92a Targets SERTAD3 and Regulates the Growth, Invasion, and Migration of Prostate Cancer Cells via the P53 Pathway
Abstract
Shuo Zhang,1,2 Jia Yu,2,3 Bao-fei Sun,1,2 Gui-zhong Hou,1 Zi-Jiang Yu,1,2 Heng Luo1– 3 1Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University, Guizhou, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 3Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, People’s Republic of ChinaCorrespondence: Heng Luo; Zi-Jiang Yu Email [email protected]; [email protected]: The miR-17-92 cluster, consisting of six mature miRNAs including miR-17, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a, plays a key role in the tumorigenesis and development of various cancers. The dysregulation of the cluster correlates with the biological mechanism of tumor growth and metastasis in vivo. However, the relationship between miR-17-92 cluster and malignancy of prostate cancer remains unclear, and its regulatory mechanism is worth investigating for controlling the proliferation and invasion of prostate cancer.Materials and Methods: The expressions of miR-17-92 cluster members were measured using real-time quantitative RT-PCR. WB and real-time quantitative RT-PCR were used to detect the expression of SERTAD3, p38, p21, p53 protein levels and transcription levels. Cell proliferation and apoptosis were evaluated using cell proliferation assay, EdU and Hoechst assay, colony formation experiment and flow cytometry analyses. Cell migration and invasion were determined via transwell assays. The TargetScan, miRDB, starBase databases and luciferase reporter assays were used to confirm the target gene of miR-92a.Results: The relative expression of miR-92a was threefold higher in the metastatic PC-3 cells compared with the non-metastatic LNCaP cells. Down-regulation of miR-92a in PC-3 cells led to the inhibition of cell proliferation, migration, and invasion, while its overexpression in LNCaP cells resulted in the promotion of cell proliferation, migration, and invasion. The role of SERTAD3 in prostate cancer can be alleviated by miR-92a inhibitor.Conclusion: SERTAD3 was the direct target gene of miR-92a in prostate cancer cells; inhibition of SERTAD3-dependent miR-92a alleviated the growth, invasion, and migration of prostate cancer cells by regulating the expression of the key genes of the p53 pathway, including p38, p53 and p21. These results suggested that targeting SERTAD3 by the induction of overexpression of miR-92a may be a treatment option in prostate cancer.Keywords: miR-92a, SERTAD3, prostate cancer, cell growth, metastasis
