title: MicroRNA-335 and -543 suppress bone metastasis in prostate cancer via targeting endothelial nitric oxide synthase.
abstract: Skeletal metastasis is the major problem in the management of prostate cancer (PCa). Even though the regulatory role of microRNAs (miRNAs) in the control of tumor metastases has been well described in numerous types of cancer, the importance in bone metastasis of PCa remains largely unknown. In the present study, the differentially expressed miRNAs were identified between the primary PCa and bone metastatic PCa samples by comparing their expression profiling using miRNA microarray, and 4 miRNAs (miR‑335, ‑543, ‑196 and ‑19a) were noted to be significantly downregulated in bone metastasis compared with primary PCa. Among those, the downregulation of 2 miRNAs (miR‑335 and ‑543) was confirmed in a total of 20 paired primary PCa and bone metastasis samples using reverse transcription‑quantitative polymerase chain reaction. Using the online target prediction tool, endothelial nitric oxide synthase (eNOS) was found to be a shared target of miR‑335 and ‑543, which was further verified using the luciferase assay. By examining the expression pattern of eNOS in primary PCa and skeletal metastatic samples, the mRNA and protein expression levels of eNOS were markedly upregulated in the metastatic samples. Furthermore, exogenous overexpression of miR‑335 and ‑543 significantly downregulated the expression level of eNOS, and substantially compromised the ability of migration and invasion in vitro. These findings suggested that miR‑335 and ‑543 are associated with bone metastasis of PCa and indicated that they may have important roles in the bone metastasis, which may also be clinically used as novel biomarkers in discriminating the different stages of human PCa and predicting bone metastasis.
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Qizhong
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of Urology, Zhongshan Hospital of Dalian University, Dalian, Liaoning 116001, P.R. China.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Dong
mesh_terms: D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: C556347:MIRN335 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III