miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy.
miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy.
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DOI：
10.18632/oncotarget.3070
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发表时间：
2015-02-20
期刊：
影响因子：
--
通讯作者：
Kunz M
中科院分区：
文献类型：
--
作者：
Bhattacharya A;Schmitz U;Raatz Y;Schönherr M;Kottek T;Schauer M;Franz S;Saalbach A;Anderegg U;Wolkenhauer O;Schadendorf D;Simon JC;Magin T;Vera J;Kunz M
本研究确定miR-638是与原发性黑色素瘤相比在黑色素瘤转移病灶中最显著过表达的miRNA之一。miR-638增强了体外黑色素瘤细胞的致瘤性和体内肺定植。mRNA表达谱鉴定了新的候选基因，包括TP 53 INP 2作为miR-638靶点，其中大部分参与p53信号传导。TP 53 INP 2的过表达严重减弱了黑色素瘤细胞的增殖和侵袭能力，这被miR-638逆转。miR-638的耗尽刺激p53和p53下游靶基因的表达，并诱导凋亡和自噬。miR-638启动子分析鉴定了miR-638靶转录因子相关蛋白2α（TFAP 2A/AP-2α）作为miR-638的直接负调控因子，提示存在双负调控反馈环。总之，miR-638支持黑色素瘤进展并抑制p53介导的凋亡途径、自噬和转录抑制因子TFAP 2A/AP-2α的表达。
The present study identified miR-638 as one of the most significantly overexpressed miRNAs in metastatic lesions of melanomas compared with primary melanomas. miR-638 enhanced the tumorigenic properties of melanoma cells in vitro and lung colonization in vivo. mRNA expression profiling identified new candidate genes including TP53INP2 as miR-638 targets, the majority of which are involved in p53 signalling. Overexpression of TP53INP2 severely attenuated proliferative and invasive capacity of melanoma cells which was reversed by miR-638. Depletion of miR-638 stimulated expression of p53 and p53 downstream target genes and induced apoptosis and autophagy. miR-638 promoter analysis identified the miR-638 target transcription factor associated protein 2α (TFAP2A/AP-2α) as a direct negative regulator of miR-638, suggestive for a double-negative regulatory feedback loop. Taken together, miR-638 supports melanoma progression and suppresses p53-mediated apoptosis pathways, autophagy and expression of the transcriptional repressor TFAP2A/AP-2α.
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影响因子：
8
作者：
Bhattacharya, A.;Schmitz, U.;Kunz, M.
通讯作者：
Kunz, M.
影响因子：
50.3
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作者：
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作者：
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通讯作者：
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影响因子：
14.9
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