MiR-601 inhibits proliferation, migration and invasion of prostate cancer stem cells by targeting KRT5 to inactivate the Wnt signaling pathway.

ABSTRACT: OBJECTIVE:This study aimed to verify the hypothesis that downregulation of miR-601 inhibits the proliferation, migration, and invasion of prostate cancer stem cells (PCSCs) by the Wnt signaling pathway through targeting keratin 5 (KRT5). METHODS:Bioinformatic tools were applied to predict miRNAs and genes potentially associated with prostate cancer, then miR-601 and KRT5 were selected. Subsequently, PCSCs were investigated with respect to miR-601 overexpression or inhibition, KRT5 overexpression, or treatment with a Wnt pathway inhibitor. A series of experiments including western blotting, RT-qPCR, wound healing experiment, transwell assay, MTT assay, annexin V-FITC/PI flow cytometric analysis, nude mice assay and immunohistochemistry were then carried out. RESULTS:Compared with negative control group, migration, invasion, and proliferation of PCSCs and Wnt-1 expression were all enhanced, but apoptosis was attenuated in the miR-601 mimic group. Furthermore, results identified in the other groups (KRT5, miR-601 inhibitor, miR-601 inhibitor + KRT5, Wnt signaling pathway inhibitor, PRI-724/PRI-724 + KRT5) were opposite to those identified with the miR-601 mimic group (all P<0.05). Compared with the miR-601 inhibitor + KRT5 group, migration, invasion, and proliferation of PCSCs and Wnt-1 expression were all increased, whereas apoptosis was suppressed in KRT5 or miR-601 inhibitor groups (all P<0.05). Compared with the PRI-724 + KRT5 group, migration, invasion, and proliferation of PCSCs and Wnt-1 expression were also enhanced, whereas apoptosis was inhibited in PRI-724 or KRT5 groups (all P<0.05). CONCLUSION:Results obtained from the present study have demonstrated that downregulation of miR-601 is able to inhibit the proliferation, migration, and invasion of PCSCs by activating KRT5, and subsequently inhibiting the Wnt pathway.

SUBMITTER: Du H 

PROVIDER: S-EPMC6949885 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature