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A schematic diagram of the systematic strategies for uncovering the involvement of miR-30d in human prostate cancer (PCa). Figure S2. miR-30d expression in human PCa cell lines (A) and clinical PCa tissues (B). Data were presented as Mean Âą SD. **P

The sequences of all the primers. Table S2. The antibodies of all proteins. Table S3. Associations of miR-30d expression with various clinicopathological parameters of PCa patients based on Taylor and TCGA datasets. Table S4. Univariate and multivariate analyses on prognostic implications of various clinicopathological parameters of human PCa based on Taylor dataset. Table S5. One hundred and forty-six differentially expressed gene with more than 2 ratio both in LNCaP and DU145 cells from gene expression profile. Table S6. Thirty-six putative targets of miR-30d which were also downregulated in both miR-30d-transfected LNCaP and DU145 cells according to the gene microarray analysis. Table S7. The pathway enrichment analysis based on KEGG database. Table S8. Associations of MYPT1 protein expression with clinicopathological characteristics of PCa patients. Table S9. Cox proportional hazards multivariate model for evaluating the prognostic values of various factors in human prostate cancer based on Taylor dataset. Table S10. Associations between MYPT1 expression in PCa tissues and Gleason score. Table S11. Associations between miR-30d expression in PCa tissues and Gleason score based on Taylor and TCGA datasets. (DOCX 58 kb)

Background Even though aberrant expression of microRNA (miR)-30d has been reported in prostate cancer (PCa), its associations with cancer progression remain contradictory. The aim of this study was to investigate clinical significance, biological functions and underlying mechanisms of miR-30d deregulation in PCa. Methods Involvement of miR-30d deregulation in malignant phenotypes of PCa was demonstrated by clinical sample evaluation, and in vitro and in vivo experiments. The mechanisms underlying its regulatory effect on tumor angiogenesis were determined. Results miR-30d over-expression was observed in both PCa cells and clinical specimens. High-miR-30d was distinctly associated with high pre-operative PSA and Gleason score, advanced clinical and pathological stages, positive metastasis and biochemical recurrence (BCR), and reduced overall survival of PCa patients. Through gain- and loss-of-function experiments, we found that miR-30d promoted PCa cell proliferation, migration, invasion, and capillary tube formation of endothelial cells, as well as in vivo tumor growth and angiogenesis in a mouse model. Simulation of myosin phosphatase targeting subunit 1 (MYPT1), acting as a direct target of miR-30d, antagonized the effects induced by miR-30d up-regulation in PCa cells. Notably, miR-30d/MYPT1 combination was identified as an independent factor to predict BCR of PCa patients. Furthermore, miR-30d exerted its pro-angiogenesis function, at least in part, by inhibiting MYPT1, which in turn, increased phosphorylation levels of c-JUN and activated VEGFA-induced signaling cascade in endothelial cells. Conclusions miR-30d and/or its target gene MYPT1 may serve as novel prognostic markers of PCa. miR-30d promotes tumor angiogenesis of PCa through MYPT1/c-JUN/VEGFA pathway. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0615-x) contains supplementary material, which is available to authorized users.

File S1. for the manuscript titled as â MicroRNA-30d promotes angiogenesis and tumor growth via MYPT1/c-JUN/VEGFA pathway and predicts aggressive outcome in prostate cancerâ . (DOC 38 kb)

File S1. for the manuscript titled as â MicroRNA-30d promotes angiogenesis and tumor growth via MYPT1/c-JUN/VEGFA pathway and predicts aggressive outcome in prostate cancerâ . (DOC 38 kb)

The sequences of all the primers. Table S2. The antibodies of all proteins. Table S3. Associations of miR-30d expression with various clinicopathological parameters of PCa patients based on Taylor and TCGA datasets. Table S4. Univariate and multivariate analyses on prognostic implications of various clinicopathological parameters of human PCa based on Taylor dataset. Table S5. One hundred and forty-six differentially expressed gene with more than 2 ratio both in LNCaP and DU145 cells from gene expression profile. Table S6. Thirty-six putative targets of miR-30d which were also downregulated in both miR-30d-transfected LNCaP and DU145 cells according to the gene microarray analysis. Table S7. The pathway enrichment analysis based on KEGG database. Table S8. Associations of MYPT1 protein expression with clinicopathological characteristics of PCa patients. Table S9. Cox proportional hazards multivariate model for evaluating the prognostic values of various factors in human prostate cancer based on Taylor dataset. Table S10. Associations between MYPT1 expression in PCa tissues and Gleason score. Table S11. Associations between miR-30d expression in PCa tissues and Gleason score based on Taylor and TCGA datasets. (DOCX 58 kb)