MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP
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DOI:
10.1159/000464120
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发表时间:
2017-01-01
影响因子:
--
通讯作者:
Xiao, Cheng-cheng
Xiao, Cheng-cheng
中科院分区:
医学1区
文献类型:
--
作者:
Du, Yang;Zhu, Heng-cheng;Xiao, Cheng-cheng

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背景/目的:微小RNA(miRNAs,miRs)已成为各种癌症中重要的转录后调节因子。miR-543在肝细胞癌和结直肠癌中发挥重要作用,但其在前列腺癌发病机制中的作用尚不完全清楚。研究方法:miR-543和Raf激酶抑制蛋白(RKIP)在临床前列腺癌标本中的表达,测定两种前列腺癌细胞系,即LNCAP和C4-2B。还通过体外和体内研究研究了miR-543对肿瘤细胞增殖和转移的影响。结果如下:发现miR-543与临床肿瘤样品中的RKIP表达呈负相关,并且与亲本LNCAP细胞相比,在转移性前列腺癌细胞系C4-2B中显著上调。进一步的研究将RKIP确定为miR-543的直接靶点。miR-543过表达可下调RKIP的表达,促进癌细胞的增殖和转移;而敲低miR-543则可上调RKIP的表达,抑制癌细胞的增殖和转移。结论:miR-543通过靶向RKIP促进前列腺癌的增殖和转移。(C)2017作者(S)
Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP. (C) 2017 The Author(s)