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Clinical and Translational Oncology

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01-05-2017 | Research Article

Biological function and mechanism of miR-33a in prostate cancer survival and metastasis: via downregulating Engrailed-2

Authors: Q. Li, S. Lu, X. Li, G. Hou, L. Yan, W. Zhang, B. Qiao

Published in: Clinical and Translational Oncology | Issue 5/2017

Abstract

Objective

Recent studies have identified Engrailed-2 (EN-2), a homeobox-containing transcription factor, as a candidate oncogene in prostate cancer (PC). Therapeutic targeting on EN-2, however, is limited because the mechanism underlying EN-2 overexpression in prostatic cancer cells is unknown. This study was to investigate the potential regulatory role of miR-33a on EN-2 expression and explore this signaling axis in ability of prostate cancer survival and metastasis.

Methods

The relative expression of miR-33a and EN-2 in paired prostate cancer tissue and adjacent normal tissue as well as in prostate cancer cell lines, PC3 and DU145, was determined using quantitative real-time PCR or western blot, respectively. Cells survival, migration and invasion were evaluated by assays of MTT, TUNEL and Boyden chamber assays, respectively. Direct regulation of EN-2 by miR-33a was examined by luciferase reporter assay.

Results

The data showed that miR-33a was upregulated and EN-2 was downregulated in both prostate cancer tissue and prostate cancer cells. miR-33a overexpression suppresses prostate cancer cell survival and metastasis. miR-33a can directly act on EN-2 expression by binding to 3′UTR of its mRNA. Also, miR-33a negatively regulated EN-2 mRNA and protein expression. In pcDNA-EN-2 and miR-33a mimic co-transfected PC3 and DU145 cells, EN-2 overexpression reverses the anti-cell survival and metastasis actions of miR-33a overexpression. The pivotal role of miR-33a in inhibiting prostate tumor growth was confirmed in xenograft models of prostate cancer.

Conclusion

Our data suggest that the functional interaction of miR-33a and EN-2 is involved in tumorigenesis of prostate cancer. Also in this process EN-2 serves as a negative responder for miR-33a.

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Title: Biological function and mechanism of miR-33a in prostate cancer survival and metastasis: via downregulating Engrailed-2
Authors: Q. Li
S. Lu
X. Li
G. Hou
L. Yan
W. Zhang
B. Qiao
Publication date: 01-05-2017
Publisher: Springer International Publishing
Published in: Clinical and Translational Oncology / Issue 5/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-016-1564-3

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Abstract

Objective

Methods

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Conclusion

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