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

Abstract

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-β (TGF-β), TGF-β receptor 1 (TGF-βR1), and p53 or phosphorylation levels of mothers against decapentaplegic 3 (SMAD3) in the TGF-β/Smad3 signaling pathway have yet to be elucidated, and will provide novel tools for diagnosis and treatment of metastatic PCa.

MiR‐34b‐3p represses cell proliferation, cell cycle progression and cell apoptosis in non‐small‐cell lung cancer (NSCLC) by targeting CDK4

“…Aberrant miRNA expression is related to various biological processes, such as proliferation, apoptosis, angiogenesis, migration and invasion. Human miR‐34b‐3p is down‐regulated in several cancer types, such as small lung cancer cell (SCLC), breast cancer and prostate cancer . This observation suggests that miR‐34b‐3p might play a key role in tumourigenesis.…”

Fli-1 Activation through Targeted Promoter Activity Regulation Using a Novel 3’, 5’-diprenylated Chalcone Inhibits Growth and Metastasis of Prostate Cancer Cells

“…The cell transfer ability was measured via an in vitro scratch repair assay [43]. PC3 cells in logarithmic growth phase were seeded into a 6-well plate at a concentration of 50,000 cells per well and incubated at 37 • C for 24 h. When PC3 cells attached and grew to about 80%, we made scratched lines and added different concentrations (0, 0.5, 1.0, and 2.0µmol/L) of C10 and incubated for 12 h and 24 h. The repair ability was observed using an inverted fluorescence microscope.…”

“…Transwell chamber invasion assay was used to examine the effect of C10 on the invasion capability of PC3 cells [43]. First, Matrigel ® Matrix (Invitrogen, Carlsbad, CA, USA) was thawed overnight at 4 • C, and diluted in serum-free DMEM to a final concentration of 1 mg/mL.…”

TGF-β and microRNA Interplay in Genitourinary Cancers

“…Complex regulation of the TGF-β signaling pathway is exerted by miR-34b, which modulates expressions of TGF-β, TGFBR1, and pSMAD4, p53. Transfection of PC3 prostate cancer cells with miR-34b mimics results in the inhibition of cell growth, migration, and invasion [306]. The expression of SMAD4 is also regulated by multiple other microRNAs, including miR-1260b, miR-301a, miR-888, and miR-183 [307][308][309][310][311].…”