MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms.
MiR-10a and HOXB4 are overexpressed in atypical myeloproliferative neoplasms.
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DOI：
10.1186/s12885-018-4993-2
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发表时间：
2018-11-12
期刊：
影响因子：
3.8
通讯作者：
Lippert E
中科院分区：
文献类型：
--
作者：
Dumas PY;Mansier O;Prouzet-Mauleon V;Koya J;Villacreces A;Brunet de la Grange P;Luque Paz D;Bidet A;Pasquet JM;Praloran V;Salin F;Kurokawa M;Mahon FX;Cardinaud B;Lippert E
非典型骨髓增生性肿瘤（aMPN）具有MPN和骨髓增生异常综合征的共同特征。虽然细胞因子信号异常在MPN中很常见，但非典型MPN的病理生理学仍然难以捉摸。由于microRNA的失调涉及各种癌症的生物学，我们研究了aMPN患者的miRNome。在aMPN患者中探索MiRNome和表观遗传调节基因ASXL 1、TET 2、DNMT 3A、EZH 2和IDH 1/2的突变。通过用5-氮杂-2 '脱氧胞苷、丙戊酸和视黄酸处理造血细胞系来研究miR-10a和HOXB 4表达的表观遗传调控。通过用编码pri-miR-10a前体的慢病毒载体转导CD 34+细胞来研究miR-10a过表达对细胞增殖、分化和自我更新的功能性影响。miR-10a被鉴定为aMPN中最显著上调的microRNA。miR-10a的表达与HOXB 4的表达相关，位于相同的基因组位点。这两个基因的转录增加了DNA去甲基化和组蛋白乙酰化，这两个必要的最佳表达诱导视黄酸。此外，miR-10a和HOXB 4过表达似乎与血液恶性肿瘤中的DNMT 3A突变相关。然而，过表达miR-10a对正常造血祖细胞的增殖、分化或自我更新没有影响。miR-10a和HOXB 4在aMPN中过表达。这种过度表达似乎是表观遗传调节机制异常的结果。我们的数据表明，miR-10a可以代表在这个基因组位点（包括HOXB 4）的简单转录标记，HOXB 4被广泛认为参与干细胞扩增。本文的在线版本（10.1186/s12885-018-4993-2）包含补充材料，可供授权用户使用。
Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes. Although abnormalities in cytokine signaling are common in MPN, the pathophysiology of atypical MPN still remains elusive. Since deregulation of microRNAs is involved in the biology of various cancers, we studied the miRNome of aMPN patients. MiRNome and mutations in epigenetic regulator genes ASXL1, TET2, DNMT3A, EZH2 and IDH1/2 were explored in aMPN patients. Epigenetic regulation of miR-10a and HOXB4 expression was investigated by treating hematopoietic cell lines with 5-aza-2’deoxycytidine, valproic acid and retinoic acid. Functional effects of miR-10a overexpression on cell proliferation, differentiation and self-renewal were studied by transducing CD34+ cells with lentiviral vectors encoding the pri-miR-10a precursor. MiR-10a was identified as the most significantly up-regulated microRNA in aMPN. MiR-10a expression correlated with that of HOXB4, sitting in the same genomic locus. The transcription of these two genes was increased by DNA demethylation and histone acetylation, both necessary for optimal expression induction by retinoic acid. Moreover, miR-10a and HOXB4 overexpression seemed associated with DNMT3A mutation in hematological malignancies. However, overexpression of miR-10a had no effect on proliferation, differentiation or self-renewal of normal hematopoietic progenitors. MiR-10a and HOXB4 are overexpressed in aMPN. This overexpression seems to be the result of abnormalities in epigenetic regulation mechanisms. Our data suggest that miR-10a could represent a simple marker of transcription at this genomic locus including HOXB4, widely recognized as involved in stem cell expansion. The online version of this article (10.1186/s12885-018-4993-2) contains supplementary material, which is available to authorized users.
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影响因子：
37.3
作者：
Bryant A;Palma CA;Jayaswal V;Yang YW;Lutherborrow M;Ma DD
通讯作者：
Ma DD
影响因子：
20.3
作者：
Havelange, Violaine;Ranganathan, Parvathi;Garzon, Ramiro
通讯作者：
Garzon, Ramiro
影响因子：
2.6
作者：
Guglielmelli, Paola;Tozzi, Lorenzo;Vannucchi, Alessandro M.
通讯作者：
Vannucchi, Alessandro M.
影响因子：
45.3
作者：
Gale, Rosemary E.;Lamb, Katarina;Linch, David C.
通讯作者：
Linch, David C.
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK