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OBJECTIVE: SCCRO/DCUN1D1/DCN1 (squamous cell carcinoma-related oncogene/defective in cullin neddylation 1 domain containing 1/defective in cullin neddylation) is considered as an oncogene, but its role in the prostate cancer (PC) is still not clear. The current study aims to investigate the expression of SCCRO in PC tumor tissues, further its clinical significance, and proliferation inhibiting effect on PC cells in vitro. PATIENTS AND METHODS: RT-PCR was used to detect the expression of SCCRO in PC tissue and corresponding adjacent normal tissues from 160 cases, and its relationship with clinical pathological characteristics was analyzed. Small interfering RNA (siRNA) expression plasmid targeting SCCRO gene was constructed and transferred into PC cell line Lncap. The effect on proliferation was observed by CCK8 assay, and its influence on invasion and migration of Lncap cells was studied by Transwell Matrigel assay after SCCRO gene was silenced. The expression of focal adhesion kinase (FAK) and matrix metalloproteinase- 2 (MMP-2) influenced by SCCRO silencing were detected by Western blot. RESULTS: mRNA expression of SCCRO protein increased significantly in cancer tissues compared to adjacent normal tissue, especially for T3+T4, N+, and III+IV patients (p<0.05). SCCRO expression was an independent prognostic factor (p<0.05). After SCCRO gene was knocked down by siRNA, the SCCRO protein level decreased 78.4% in the siRNA-3 group. By CCK8 assay, knocking down SCCRO in Lncap significantly reduced the cell proliferation, as well as its migration and invasion capability compared to siRNA-control group (p<0.01) by transwell invasion and migration assay. The expression of FAK and MMP-2 also reduced in siRNA-3 group compared to siRNA control group (p<0.01). CONCLUSIONS: SCCRO is associated with progression and prognosis of PC. After SCCRO gene was transferred, the growth of Lncap cells was inhibited, and ability of invasion and migration decreased by reducing the expression of FAK and MMP-2. SCCRO has potential to become a new target for the treatment of PC. [ABSTRACT FROM AUTHOR]