title: Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT.
abstract: The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis.
authors.affiliation: Department of Orthopaedic Surgery/Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. pengxs66@yahoo.com
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Peng
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Tiejian
authors.initials: T
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Xiang'an
authors.initials: X
authors.lastname: Tu
authors.forename: Dafu
authors.initials: D
authors.lastname: Xiong
authors.forename: Song
authors.initials: S
authors.lastname: Chen
authors.forename: Yingrong
authors.initials: Y
authors.lastname: Lai
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.forename: Guangfu
authors.initials: G
authors.lastname: Chen
authors.forename: Guanglin
authors.initials: G
authors.lastname: Liu
authors.forename: Yubo
authors.initials: Y
authors.lastname: Tang
authors.forename: Shuai
authors.initials: S
authors.lastname: Huang
authors.forename: Xuenong
authors.initials: X
authors.lastname: Zou
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D015203:Reproducibility of Results; D015854:Up-Regulation
chemical_list: C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D017430:Prostate-Specific Antigen