MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer
MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer
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Microrna-494-3p 以 Cxcr4 为靶点，抑制前列腺癌的增殖、侵袭和迁移。
DOI：
10.1002/pros.22795
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发表时间：
2014-05-01
期刊：
影响因子：
2.8
通讯作者：
Zeng, Hao
中科院分区：
文献类型：
--
作者：
Shen, Peng-fei;Chen, Xue-qin;Zeng, Hao
背景虽然SDF-1/CXCR 4通路是肿瘤增殖和进展的一个潜在机制，但其调控CXCR 4表达的机制尚不完全清楚。本研究旨在证实miR-494- 3 p可能是CXCR 4的一个潜在的转录后调节因子，过表达miR-494可能抑制前列腺癌的进展和转移。通过双报告基因分析证实miR-494- 3 p可通过与预测位点结合，对CXCR 4 mRNA进行转录后调控。通过MTT、TUNEL、流式细胞术、迁移和侵袭实验检测miR-494- 3 p对前列腺癌细胞增殖、凋亡、迁移和侵袭的生物学效应。结果显示，在PC-3和DU 145中，CXCR 4的mRNA和蛋白表达水平显著上调，而在LNCaP和RWPE-1中几乎未检测到。然而，在RWPE-1和前列腺癌细胞中，CXCR 4蛋白水平与成熟miR-494- 3 p表达水平呈负相关。miR-494- 3 p的组成性过表达可下调PC-3和DU 145中CXCR 4的蛋白水平。miR-494- 3 p也能与CXCR 4基因的3 '-UTR中的种子序列结合。结论miR-494 - 3 p可能通过对CXCR 4 mRNA的转录后调节，在前列腺癌的发生发展中发挥重要作用。miR-494- 3 p/CXCR 4通路可能是预防前列腺癌进展和转移的潜在治疗靶点。前列腺74：756-767，2014年。(c)2014 Wiley Periodicals，Inc.
BACKGROUNDAlthough SDF-1/CXCR4 pathway is a potential mechanism of tumor proliferation and progression, the mechanism of controlling CXCR4 expression is not fully understood. This study was to confirm that miR-494-3p might be a potentially post-transcriptional regulator of CXCR4 and over-expression of miR-494 might suppress prostate cancer progression and metastasis.MATERIALS AND METHODSWe firstly postulated the post-transcriptional regulation of CXCR4 by miR-494-3p through bioinformatics analysis, and then it was demonstrated that miR-494-3p could regulate the CXCR4 mRNA post-transcriptionally by binding to the predicted site by dual reporter gene assays. The biological effect of miR-494-3p on prostate cancer cells proliferation, apoptosis, migration, and invasion was measured by MTT, TUNEL, flow cytometry, migration, and invasion assays.RESULTSIt was shown that the mRNA and protein expression levels of CXCR4 were significantly up-regulated in PC-3 and DU145, whereas barely detected in LNCaP and RWPE-1. However, the CXCR4 protein levels were inversely related to the mature miR-494-3p expression levels in RWPE-1 and prostate cancer cells. The constitutive over-expression of miR-494-3p could down-regulate the protein level of CXCR4 in PC-3 and DU145. MiR-494-3p also could bind to the seed sequences in the 3 '-UTR of the CXCR4 gene. Artificial over-expression of miR-494-3p could inhibit the growth, promote the apoptosis, and inhibit the migration and invasion of PC-3 and DU145 cells in vivo.CONCLUSIONSOur results suggested that miR-494-3p might play crucial role in prostate cancer by post-transcriptional regulation to CXCR4 mRNA. MiR-494-3p/CXCR4 pathway may be a potential therapeutic target to prevent prostate cancer progression and metastasis. Prostate 74:756-767, 2014. (c) 2014 Wiley Periodicals, Inc.