STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-I-Transformed and ATL Cells.
STAT1: A Novel Target of miR-150 and miR-223 Is Involved in the Proliferation of HTLV-I-Transformed and ATL Cells.
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DOI：
10.1016/j.neo.2015.04.005
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发表时间：
2015-05
期刊：
影响因子：
4.8
通讯作者：
Nicot, Christophe
中科院分区：
文献类型：
--
作者：
Moles, Ramona;Bellon, Marcia;Nicot, Christophe
我们以前曾报道过在人类T细胞嗜淋巴细胞病毒1型（HTLV-I）转化细胞中参与造血和炎症的细胞microRNA的失调。在这项研究中，我们证明了miR-150和miR-223特异性靶向信号转导和转录激活因子1（STAT1）3 ′非翻译区，减少STAT1表达，抑制人T细胞中STAT1依赖性信号传导。使用诱导型细胞系证实了miR-150和miR-223对内源性STAT1的作用。我们的研究还表明，miR-150的表达上调的白细胞介素-2信号在成人T细胞白血病/淋巴瘤（ATL）细胞。HTLV-I转化的和ATL衍生的细胞具有降低的miR150和miR223表达水平，这与增加的STAT1表达和STAT1依赖性信号传导相一致。通过短发夹RNA敲低STAT1表明，STAT1的组成性激活是HTLV-I转化细胞持续增殖所必需的。我们的研究进一步表明，ATL细胞中STAT1表达的增加与I类主要组织相容性复合体表达水平的升高有关。先前的研究已经证明，自然杀伤（NK）细胞在体内施加的压力可以通过迫使主要组织相容性复合物I类的表达增加来逃避免疫清除来编辑白血病肿瘤细胞。表达STAT1的肿瘤细胞产生更具侵袭性的肿瘤，因为它们不能被NK细胞消除。我们的研究结果表明，联合靶向STAT1和MHC I类分子的治疗方法可能是激活NK细胞介导的ATL肿瘤细胞清除的有效方法。
We have previously reported on the deregulation of cellular microRNAs involved in hematopoiesis and inflammation in human T-cell lymphotropic virus type 1 (HTLV-I)–transformed cells. In this study, we demonstrate that miR-150 and miR-223 specifically target the signal transducer and activator of transcription 1 (STAT1) 3′ untranslated region, reducing STAT1 expression and dampening STAT1-dependent signaling in human T cells. The effects of miR-150 and miR-223 on endogenous STAT1 were confirmed using inducible cell lines. Our studies also showed that miR-150 expression is upregulated by interleukin-2 signaling in adult T cell leukemia/lymphoma (ATL) cells. HTLV-I–transformed and ATL-derived cells have reduced levels of miR150 and miR223 expression, which coincide with increased STAT1 expression and STAT1-dependent signaling. Knockdown of STAT1 by short hairpin RNA demonstrated that the constitutive activation of STAT1 is required for the continuous proliferation of HTLV-I–transformed cells. Our studies further demonstrate that increased expression of STAT1 in ATL cells is associated with higher levels of major histocompatibility complex class I expression. Previous studies have demonstrated that the pressure exerted by natural killer (NK) cells in vivo can edit leukemic tumor cells by forcing an increased expression of major histocompatibility complex class I to escape immune clearance. STAT1-expressing tumor cells produce more aggressive tumors because they cannot be eliminated by NK cells. Our results suggest that therapeutic approaches using combined targeting of STAT1 and MHC class I may be an effective approach to activate NK cell–mediated clearance of ATL tumor cells.
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影响因子：
3.7
作者：
Huang S;Chen Y;Wu W;Ouyang N;Chen J;Li H;Liu X;Su F;Lin L;Yao Y
通讯作者：
Yao Y
影响因子：
3.8
作者：
Avery-Kiejda KA;Braye SG;Mathe A;Forbes JF;Scott RJ
通讯作者：
Scott RJ
RA诱导基因-I诱导增强STAT1激活以抑制白血病细胞增殖
DOI：
10.1073/pnas.1019059108
发表时间：
2011-02-01
影响因子：
11.1
作者：
Jiang, Lin-Jia;Zhang, Nan-Nan;Zhu, Jiang
通讯作者：
Zhu, Jiang
影响因子：
3
作者：
Gessain, A.;Mahieux, R.
通讯作者：
Mahieux, R.
DOI：
10.4161/jkst.20045
发表时间：
2012-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Avalle L;Pensa S;Regis G;Novelli F;Poli V
通讯作者：
Poli V