Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1.
Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1.
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DOI：
10.1158/0008-5472.can-08-0769
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发表时间：
2008-11-01
期刊：
影响因子：
11.2
通讯作者：
Jeang KT
中科院分区：
文献类型：
--
作者：
Yeung ML;Yasunaga J;Bennasser Y;Dusetti N;Harris D;Ahmad N;Matsuoka M;Jeang KT
miRNA在人T细胞白血病病毒-1（HTLV-1）介导的细胞转化中的作用尚未描述。在这里，我们分析了HTLV-1转化的人T细胞系和成人T细胞白血病（ATL）患者的原代外周血单核细胞（PBMC）中的miRNA表达。对11个不同谱的分析揭示了6个一致上调的miRNAs。两种上调的miRNAs（miR-93和miR-130 b）靶向肿瘤抑制蛋白（肿瘤蛋白53诱导的核蛋白1（TP 53 INP 1））mRNA的3′非翻译区（3′UTR）。HTLV-1转化细胞中TP 53 INP 1蛋白的表达水平较低。此外，当使用阿托咪来敲低这些细胞中的miR-93和miR-130 b时，TP 53 INP 1的表达增加，表明后者在细胞内由前者调节。通过实验确定了TP 53 INP 1在调节细胞生长中的作用，所述实验表明增强的TP 53 INP 1表达增加了凋亡。总的来说，这些发现涉及影响HTLV-1感染/转化细胞的增殖和存活的miR-93/miR-130 b-TP 53 INP 1轴。
A role for miRNAs in human T-cell leukemia virus-1, HTLV-1, mediated cellular transformation has not been described. Here, we profiled miRNA expression in HTLV-1 transformed human T cell lines and primary peripheral blood mononuclear cells (PBMCs) from Adult-T cell leukemia (ATL) patients. Analyses of eleven different profiles revealed six miRNAs which were consistently up-regulated. Two of the up-regulated miRNAs (miR-93 and miR-130b) target the 3′ untranslated region (3′UTR) of the mRNA for a tumor suppressor protein, Tumor Protein 53-Induced Nuclear Protein 1 (TP53INP1). A low expression level of TP53INP1 protein was found in HTLV-1 transformed cells. Additionally, when antagomirs were used to knock down miR-93 and miR-130b in these cells, the expression of TP53INP1 was increased suggesting that the latter is regulated inside cells by the former. A role for TP53INP1 in regulating cell growth was established by experiments which showed that enhanced TP53INP1 expression increased apoptosis. Collectively, the findings implicate a miR-93/miR-130b – TP53INP1 axis that impacts the proliferation and survival of HTLV-1 infected / transformed cells.