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Biomed Pharmacother. 2018 Jan;97:120-127. doi: 10.1016/j.biopha.2017.10.115. Epub 2017 Nov 6.

Suppression of microRNA-454 impedes the proliferation and invasion of prostate cancer cells by promoting N-myc downstream-regulated gene 2 and inhibiting WNT/β-catenin signaling.

Author information

1
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
2
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China. Electronic address: wang_hewh@163.com.
3
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China. Electronic address: binsong_bs@163.com.
4
Department of Urology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, China. Electronic address: xin_lilx@163.com.

Abstract

MicroRNA-454 (miR-454) is emerging as critical regulator in tumorigenesis; it may function as an oncogene or a tumor suppressor. However, the role of miR-454 in prostate cancer remains unknown. In this study, we aimed to investigate the function and molecular mechanisms of miR-454 in prostate cancer. We found that miR-454 was highly expressed in prostate cancer tissues and cell lines (*p<0.05), as detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 assay, colony formation assay and cell invasion assay showed that the inhibition of miR-454 significantly suppressed prostate cancer cell proliferation and invasion (*p<0.05), whereas the overexpression of miR-454 markedly promoted prostate cancer cell proliferation and invasion (*p<0.05). Bioinformatics analysis showed that N-myc downstream-regulated gene 2 (NDRG2), a well-known tumor suppressor, was identified as a potential target gene of miR-454. Dual-luciferase reporter assay showed that miR-454 directly targeted the 3'-untranslated region of NDRG2. RT-qPCR and western blot showed that miR-454 overexpression significantly decreased NDRG2 expression (*p<0.05), whereas miR-454 inhibition markedly promoted NDRG2 expression (*p<0.05). Spearman's correlation analysis showed that miR-454 expression was inversely correlated with NDRG2 expression in prostate cancer tissues (r=-0.8932; p<0.0001). Moreover, miR-454 inhibition significantly suppressed the protein expression of β-catenin (*p<0.05) and blocked the activation of WNT signaling (*p<0.05). In addition, small interfering RNA mediated NDRG2 knockdown significantly reversed the antitumor effect of miR-454 inhibition on prostate cancer cell proliferation and invasion (*p<0.05). Taken together, these results reveal an oncogenic role of miR-454, which promotes prostate cancer cell proliferation and invasion by downregulation of NDRG2. These results also suggest miR-454 as a potential therapeutic target for the treatment of prostate cancer.

KEYWORDS:

NDRG2; Prostate cancer; WNT; miR-454

PMID:
29080452
DOI:
10.1016/j.biopha.2017.10.115
[Indexed for MEDLINE]

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