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微小RNA-429通过直接靶向BMI1和E2F3抑制肾细胞癌的细胞增殖、上皮-间质转化和转移。

MicroRNA-429 suppresses cell proliferation, epithelial-mesenchymal transition, and metastasis by direct targeting of BMI1 and E2F3 in renal cell carcinoma.

作者信息

Qiu Mingning, Liang Ziji, Chen Lieqian, Tan Guobin, Wang Kangning, Liu Lei, Liu Jianjun, Chen Hege

机构信息

Laboratory of Urology, Guangdong Medical College, Zhanjiang, China.

Laboratory of Urology, Guangdong Medical College, Zhanjiang, China.

出版信息

Urol Oncol. 2015 Jul;33(7):332.e9-18. doi: 10.1016/j.urolonc.2015.03.016. Epub 2015 May 4.

DOI:10.1016/j.urolonc.2015.03.016
PMID:25953723
Abstract

BACKGROUND

MicroRNA-429 (miR-429), a short noncoding RNA belonging to the miR-200 superfamily, plays a crucial role in tumorigenesis and tumor progression. It also acts as a modulator of epithelial-to-mesenchymal transition, a cell development regulating process that affects tumor development and metastasis. The aim of this study was to investigate the potential role of miR-429 in regulating growth and metastasis of renal cell carcinoma.

METHODS

miR-429 expression was stably up-regulated or down-regulated in the renal cell carcinoma ACHN and A498 cell lines, and cell proliferation and metastasis were assessed.

RESULTS

miR-429 overexpression inhibited cell proliferation, colony formation, migration, and invasion. Suppression of endogenous miR-429 promoted cell growth and metastasis. miR-429 was shown to directly target the 3' untranslated regions of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) and E2F transcription factor 3 (E2F3) transcripts, regulating their expression, as well as that of the downstream epithelial-to-mesenchymal transition markers E-cadherin, N-cadherin, vimentin, p14, and p16.

CONCLUSIONS

These results revealed a tumor suppressive role for miR-429 in renal cell carcinoma through directly targeting BMI1 and E2F3.

摘要

背景

微小RNA - 429(miR - 429)是一种属于miR - 200超家族的短链非编码RNA,在肿瘤发生和肿瘤进展中起关键作用。它还作为上皮 - 间质转化的调节因子,上皮 - 间质转化是一种影响肿瘤发展和转移的细胞发育调节过程。本研究的目的是探讨miR - 429在调节肾细胞癌生长和转移中的潜在作用。

方法

在肾细胞癌ACHN和A498细胞系中稳定上调或下调miR - 429表达,并评估细胞增殖和转移情况。

结果

miR - 429过表达抑制细胞增殖、集落形成、迁移和侵袭。抑制内源性miR - 429促进细胞生长和转移。miR - 429被证明直接靶向B细胞特异性莫洛尼鼠白血病病毒插入位点1(BMI1)和E盒结合因子3(E2F3)转录本的3'非翻译区,调节它们的表达,以及下游上皮 - 间质转化标志物E - 钙黏蛋白、N - 钙黏蛋白、波形蛋白、p14和p16的表达。

结论

这些结果揭示了miR - 429通过直接靶向BMI1和E2F3在肾细胞癌中发挥肿瘤抑制作用。

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