MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma.
MicroRNA-9 up-regulates E-cadherin through inhibition of NF-κB1-Snail1 pathway in melanoma.
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DOI：
10.1002/path.2964
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发表时间：
2012-01
影响因子：
7.3
通讯作者：
Xu, Xiaowei
中科院分区：
文献类型：
--
作者：
Liu, Shujing;Kumar, Suresh M.;Lu, Hezhe;Liu, Aihua;Yang, Ruifeng;Pushparajan, Anitha;Guo, Wei;Xu, Xiaowei
microRNA（miRNAs）是一类短的非编码RNA，在转录后调节基因表达。Hsa-miR-9已被证明在不同的肿瘤类型中具有相反的功能;然而，潜在的机制尚不清楚。在这里，我们表明，hsa-miR-9是下调转移性黑色素瘤相比，原发性黑色素瘤。在黑色素瘤细胞中过表达miR-9导致细胞增殖和迁移能力显著降低，F-actin聚合减少，参与细胞骨架重塑的多种GTP酶下调。miR-9过表达诱导Snail 1显著下调，同时E-cadherin表达增加。相反，敲低miR-9增加Snail 1表达以及黑色素瘤细胞增殖和迁移能力。从机制上讲，miR-9表达下调了黑色素瘤中的NF-κB1，这种作用被NF-κB1 3′-非翻译区（UTR）内推定的miR-9结合位点的突变所消除。抗miR-9 miRNA抑制剂也增加NF-κB1的表达。miR-9对Snail 1表达和黑色素瘤细胞增殖和迁移的影响可通过NF-κB1在这些细胞中的过表达来挽救。此外，miR-9过表达导致体内黑色素瘤生长和转移显著降低。总之，miR-9通过下调NF-κB1-Snail 1通路抑制黑色素瘤增殖和转移。这项研究发现了miR-9降低E-cadherin表达和抑制黑色素瘤进展的新机制。结果表明，microRNA的功能是上下文和肿瘤类型特异性的。
MicroRNAs (miRNAs) are short non-coding RNAs that post-transcriptionally regulate gene expression. Hsa-miR-9 has been shown to have opposite functions in different tumour types; however, the underlying mechanism is unclear. Here we show that hsa-miR-9 is down-regulated in metastatic melanomas compared to primary melanomas. Overexpression of miR-9 in melanoma cells resulted in significantly decreased cell proliferation and migratory capacity with decreased F-actin polymerization and down-regulation of multiple GTPases involved in cytoskeleton remodelling. miR-9 overexpression induced significant down-regulation of Snail1 with a concomitant increase in E-cadherin expression. In contrast, knockdown of miR-9 increased Snail1 expression as well as melanoma cell proliferation and migration capacity. Mechanistically, miR-9 expression down-regulated NF-κB1 in melanoma and the effect was abolished by mutations in the putative miR-9 binding sites within the 3′-untranslated region (UTR) of NF-κB1. Anti-miR-9 miRNA inhibitor also increased the expression of NF-κB1. The effects of miR-9 on Snail1 expression and melanoma cell proliferation and migration were rescued by overexpression of NF-κB1 in these cells. Furthermore, miR-9 overexpression resulted in significantly decreased melanoma growth and metastasis in vivo. In summary, miR-9 inhibits melanoma proliferation and metastasis through down-regulation of the NF-κB1-Snail1 pathway. This study finds a new mechanism that miR-9 utilizes to decrease E-cadherin expression and inhibit melanoma progression. The results suggest that function of microRNAs is context and tumour type-specific.
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DOI：
10.1111/j.1750-3639.2008.00184.x
发表时间：
2009-07
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Nass D;Rosenwald S;Meiri E;Gilad S;Tabibian-Keissar H;Schlosberg A;Kuker H;Sion-Vardy N;Tobar A;Kharenko O;Sitbon E;Lithwick Yanai G;Elyakim E;Cholakh H;Gibori H;Spector Y;Bentwich Z;Barshack I;Rosenfeld N
通讯作者：
Rosenfeld N
影响因子：
5.3
作者：
Herranz, Nicolas;Pasini, Diego;Peiro, Sandra
通讯作者：
Peiro, Sandra
影响因子：
7.3
作者：
Lehmann, U.;Hasemeier, B.;Kreipe, H.
通讯作者：
Kreipe, H.
影响因子：
8
作者：
Hildebrandt, M. A. T.;Gu, J.;Wu, X.
通讯作者：
Wu, X.
影响因子：
3.5
作者：
Kawanishi, K;Doki, Y;Monden, M
通讯作者：
Monden, M