The modulation of Dicer regulates tumor immunogenicity in melanoma.
The modulation of Dicer regulates tumor immunogenicity in melanoma.
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DOI：
10.18632/oncotarget.10273
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Tomasi TB
中科院分区：
文献类型：
--
作者：
Hoffend NC;Magner WJ;Tomasi TB
微小RNA（miRs）是小型非编码RNA，通过靶向mRNA进行翻译抑制或降解来调节大多数细胞蛋白质网络。Dicer是一种III型核糖核酸内切酶，是microRNA生物合成的关键组分，是成熟microRNA产生所必需的。异常Dicer表达发生在许多癌症类型中，并与患者预后不良相关。例如，黑色素瘤中增加的Dicer表达与更具侵袭性的肿瘤（更高的肿瘤有丝分裂指数和浸润深度）和不良的患者预后相关。然而，Dicer在黑色素瘤发展和免疫逃避中的作用仍不清楚。在这里，我们报告了一个新发现的Dicer表达和肿瘤免疫原性之间的关系。为了研究Dicer在调节黑色素瘤免疫原性中的作用，进行了Dicer敲低研究。我们发现B16 F0-Dicer缺陷细胞与对照细胞相比表现出降低的肿瘤生长，并且能够诱导抗肿瘤免疫。肿瘤生长的减少在免疫缺陷NSG小鼠中被消除，并且显示依赖于CD 8 + T细胞。Dicer敲除还在黑素瘤细胞中诱导了更具响应性的免疫基因谱。进一步的研究表明，与对照细胞相比，CD 8 + T细胞优先杀死Dicer敲低的肿瘤细胞。综上所述，我们提出证据表明，在黑色素瘤中Dicer表达与肿瘤免疫原性有关。
MicroRNAs (miRs) are small non-coding RNAs that regulate most cellular protein networks by targeting mRNAs for translational inhibition or degradation. Dicer, a type III endoribonuclease, is a critical component in microRNA biogenesis and is required for mature microRNA production. Abnormal Dicer expression occurs in numerous cancer types and correlates with poor patient prognosis. For example, increased Dicer expression in melanoma is associated with more aggressive tumors (higher tumor mitotic index and depth of invasion) and poor patient prognosis. However, the role that Dicer plays in melanoma development and immune evasion remains unclear. Here, we report on a newly discovered relationship between Dicer expression and tumor immunogenicity. To investigate Dicer's role in regulating melanoma immunogenicity, Dicer knockdown studies were performed. We found that B16F0-Dicer deficient cells exhibited decreased tumor growth compared to control cells and were capable of inducing anti-tumor immunity. The decrease in tumor growth was abrogated in immunodeficient NSG mice and was shown to be dependent upon CD8+ T cells. Dicer knockdown also induced a more responsive immune gene profile in melanoma cells. Further studies demonstrated that CD8+ T cells preferentially killed Dicer knockdown tumor cells compared to control cells. Taken together, we present evidence which links Dicer expression to tumor immunogenicity in melanoma.
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影响因子：
56.9
作者：
Hahne, M;Rimoldi, D;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
--
作者：
Bian, Xiao-Jie;Zhang, Gui-Ming;Ye, Ding-Wei
通讯作者：
Ye, Ding-Wei
DOI：
10.1177/1352458514560923
发表时间：
2015-08
期刊：
Multiple sclerosis (Houndmills, Basingstoke, England)
影响因子：
--
作者：
Aung LL;Balashov KE
通讯作者：
Balashov KE
DOI：
10.1126/science.1174334
发表时间：
2009-08-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hill DA;Ivanovich J;Priest JR;Gurnett CA;Dehner LP;Desruisseau D;Jarzembowski JA;Wikenheiser-Brokamp KA;Suarez BK;Whelan AJ;Williams G;Bracamontes D;Messinger Y;Goodfellow PJ
通讯作者：
Goodfellow PJ
DOI：
10.1073/pnas.0710228105
发表时间：
2008-02-12
影响因子：
11.1
作者：
Chen, Jian-Fu;Murchison, Elizabeth P.;Wang, Da-Zhi
通讯作者：
Wang, Da-Zhi