Potent Inhibition of miR-34b on Migration and Invasion in Metastatic Prostate Cancer Cells by Regulating the TGF-β Pathway

被引:43
作者
Fang, Li-li [1 ,2 ,3 ,4 ]
Sun, Bao-fei [1 ,4 ]
Huang, Li-rong [1 ,2 ,3 ]
Yuan, Hai-bo [1 ,2 ,3 ]
Zhang, Shuo [1 ,4 ]
Chen, Jing [1 ,4 ]
Yu, Zi-jiang [1 ,4 ]
Luo, Heng [1 ,2 ,3 ]
机构
[1] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang 550014, Guizhou, Peoples R China
[2] Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550002, Guizhou, Peoples R China
[3] Chinese Acad Sci, Guiyang 550002, Guizhou, Peoples R China
[4] Guizhou Med Univ, Dept Anat, Guiyang 550000, Guizhou, Peoples R China
基金
中国博士后科学基金; 美国国家科学基金会;
关键词
invasion; migration; miR-34b; prostate cancer; TGF-beta signaling pathway; GROWTH-FACTOR-BETA; IDENTIFICATION; EXPRESSION; MICRORNAS; GENES;
D O I
10.3390/ijms18122762
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The importance of miRNAs in the progression of prostate cancer (PCa) has further been supported by the finding that miRNAs have been identified as potential oncogenes or tumor suppressors in PCa. Indeed, in eukaryotes, miRNAs have been found to regulate and control gene expression by degrading mRNA at the post-transcriptional level. In this study, we investigated the expression of miR-34 family members, miR-34b and miR-34c, in different PCa cell lines, and discussed the molecular mechanism of miR-34b in the invasion and migration of PCa cells in vitro. The difference analyses of the transcriptome between the DU145 and PC3 cell lines demonstrated that both miR-34b and -34c target critical pathways that are involved in metabolism, such as proliferation, and migration, and invasion. The molecular expression of miR-34b/c were lower in PC3 cells. Moreover, over-expression of miR-34b/c in PC3 cells caused profound phenotypic changes, including decreased cell proliferation, migration and invasion. Moreover, the players that regulate expression levels of transforming growth factor-beta (TGF-beta), TGF-beta receptor 1 (TGF-beta R1), and p53 or phosphorylation levels of mothers against decapentaplegic 3 (SMAD3) in the TGF-beta/Smad3 signaling pathway have yet to be elucidated, and will provide novel tools for diagnosis and treatment of metastatic PCa.
引用
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页数:17
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