TRIM11 Posttranscriptionally Modulated by miR-5193 Facilitates Tumor Growth and Metastasis of Prostate Cancer.

Abstract

Tripartite motif-containing protein 11 (TRIM11), an E3 ubiquitin ligase, possesses a pro-tumor property. Still, the detailed functions of TRIM11 remain not well characterized in prostate cancer. PC-3 and DU145 prostate cancer cells were transfected with small interfering RNAs (siRNAs) or lentiviruses for TRIM11 deficiency or overexpression, and microRNA-5193 (miR-5193) mimics were utilized for overexpressing miR-5193. Proliferation, apoptosis, migration, and invasion were examined through CCK-8, colony formation, flow cytometry, wound healing, and transwell assays. MAP kinase-extracellular signal-regulated kinase (MEK1/2) and extracellular signal-regulated kinase (ERK)1/2 activities were detected via immunoblotting. Murine xenograft models were established. Interactions of TRIM11 with miR-5193 were demonstrated via dual luciferase reporter. TRIM11 deficiency or miR-5193 overexpression exerted antiprostate cancer effects through suppression of proliferation, migration, and invasion as well as enhancement of apoptosis in PC-3 and DU145 cells. The mechanisms by which TRIM11 deficiency or miR-5193 overexpression involved the inactivation of MEK1/2 and ERK1/2. miR-5193 downregulated TRIM11 expressions in prostate cancer cells, and their interactions were confirmed. Further, up-regulated miR-5193 weakened the effects of TRIM11 overexpression on enhancing proliferation, migration, invasion, and activity of MEK1/2 and ERK1/2 as well as alleviating apoptosis of prostate cancer cells. In murine xenograft models, TRIM11 upregulation facilitated tumor growth, which was alleviated by miR-5193 overexpression. These findings described the oncogenic role of TRIM11 in prostate cancer biology, which was post-transcriptionally modulated by miR-5193.