MicroRNAs associated with increased AKT gene number in human lung carcinoma
MicroRNAs associated with increased AKT gene number in human lung carcinoma
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DOI：
10.1016/j.humpath.2016.04.011
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发表时间：
2016-10-01
期刊：
影响因子：
3.3
通讯作者：
Ooi, Akishi
中科院分区：
文献类型：
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作者：
Goto, Akiteru;Dobashi, Yoh;Ooi, Akishi
在3组肺癌中检测了微小RNA（miRNA）表达谱，这些肺癌通过AKT 1或AKT 2基因数量的增加进行分层。使用2000个探针的微阵列分析显示，与具有AKTd/d的二体性的癌（AKTd/d）相比，在具有AKT 1扩增或高水平多体性的癌（AKT 1+）中有87个上调的miRNA和32个下调的miRNA，以及在AKT 2基因（AKT 2+）中有123个上调的miRNA和83个下调的miRNA。总的来说，与AKTd/d相比，AKT 1+或AKT 2+中有182个miRNA上调。其中，28个miRNAs在AKT 1+和AKT 2+组中均上调，相对于AKTd/d组的log（2）比率在1.02和3.71之间，包括所有miR-200家族成员。定量实时聚合酶链反应显示，无论AKT基因的状态如何，表现出淋巴管浸润的癌细胞的miR-200 a（P = 0.0230）和miR-200 b（P = 0.0168）的表达显著降低。此外，详细的统计分析显示，在腺癌和早期癌（病理I/II期）中，miR-200 a的表达在AKT 2+组中高于AKT 1+组，并且这些差异具有统计学显著性（分别为P = 0.0334和P = 0.0239）。然而，miR-200 a的表达与其靶基因锌指E-box-binding homeobox 1（ZEB 1; P = .3801）或E-cadherin（P = .2840）（上皮-间质转化的标志物）的表达无显著相关性。这些结果表明，AKT 2可以调节miR-200 a在组织学或阶段特异性的方式，这种调节是独立的后续参与的miR-200 a在上皮间充质转化。(C)2016 Elsevier Inc. All rights reserved.
MicroRNA (miRNA) expression profiles were examined in 3 groups of lung carcinomas that had been stratified by increases in AKT1 or AKT2 gene number. Microarray analysis using 2000 probes revealed 87 miRNAs that were up-regulated and 32 down-regulated miRNAs in carcinomas harboring amplification or high-level polysomy of the AKT1 (AKT1+), as well as 123 up-regulated and 83 down-regulated miRNAs in those of the AKT2 genes (AKT2+), in comparison with carcinomas harboring disomy of both (AKTd/d). In total, 182 miRNAs were up-regulated in AKT1 + or AKT2 +, compared with AKTd/d. Among these, 28 miRNAs were up-regulated in both the AKT1 + and AKT2+ groups, with a log(2) ratio between 1.02 and 3.71 relative to AKTd/d group, including all miR-200 family members. Quantitative real-time polymerase chain reaction showed that carcinomas exhibiting lymph vessel invasion had significantly lower expression of miR-200a (P = .0230) and miR-200b (P = .0168), regardless of the status of the AKT genes. Moreover, a detailed statistical analysis revealed that, in adenocarcinoma and in the early stage of carcinomas (pathologic stage I/II), expression of miR-200a was higher in the AKT2 + group compared with the AKT1 + group, and these differences were statistically significant (P = .0334 and P = .0239, respectively). However, the expression of miR-200a was not significantly correlated with the expression of its target, the zinc finger E-box-binding homeobox 1 (ZEB1; P = .3801) or E-cadherin (P = .2840), a marker of the epithelial-mesenchymal transition. These results suggest that AKT2 can regulate miR-200a in a histology- or stage-specific manner and that this regulation is independent of subsequent involvement of miR-200a in epithelial-mesenchymal transition. (C) 2016 Elsevier Inc. All rights reserved.