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miR‐124 exhibits antiproliferative and antiaggressive effects on prostate cancer cells through PACE4 pathway
Author(s) -
Kang Shaosan,
Zhao Yansheng,
Hu Kaimeng,
Xu Chen,
Wang Lei,
Liu Jian,
Yao Anliang,
Zhang Hongmei,
Cao Fenghong
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22822
Subject(s) - du145 , prostate cancer , malignancy , prostate , cancer research , immunohistochemistry , immunocytochemistry , matrigel , cancer , medicine , cell growth , biology , pathology , lncap , genetics , angiogenesis
PACE4 plays an important role in prostate cancer (PCa) proliferation and aggression, which might provide a useful target against prostate cancer. In this study, we had strived to find some key miRNAs to decrease malignancy and invasiveness of PCa through regulating PACE4 expression. METHODS Clinically pathological analysis of immunohistochemistry/in situ hybridization was carried out to detect the relationship between PACE4 expression/miRNAs and the malignancy of prostate mass. Prostate cell lines (DU145, C4‐2, and BPH‐1) were cultured for growth curve, immunocytochemistry analysis, colony formation, Matrigel invasion, and transcriptional/translational expression assay of PACE4‐related signaling molecules for confirming the relationship. MiRNAs targeting PACE4 were predicted, validated and further‐corroborated using bio‐software, real‐time PCR, luciferase reporter assay and transfection of miRNA mimics and inhibitor. RESULTS It was suggested that PACE4 might reflect the pathological malignancy of prostate lesion from pathology analysis. Moreover, DU145 cells, the highest PACE4‐level and related TF expression indicated of the strongest malignancy and invasiveness. It was significantly found that miR‐124 was presented with the biggest odd to target PACE4‐3′UTR, the capability of decreasing PACE expression and slowing down cell growth and cell invasion. CONCLUSIONS It was clear that PACE4 level was closely associated with malignancy and invasiveness of PCa in vivo or in vitro MiR‐124, played a crucial role inhibiting PACE4 transcription thus exhibiting obvious effects of antiproliferation and antiaggression of PCa. Prostate 74:1095–1106, 2014 . © 2014 Wiley Periodicals, Inc.