信号转导子和转录激活子（STAT）-3 调节慢性淋巴细胞白血病细胞中的 microRNA 基因表达。
Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells.
机构信息
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Mol Cancer. 2013 Jun 1;12:50. doi: 10.1186/1476-4598-12-50.
BACKGROUNDS
Approximately 1,000 microRNAs (miRs) are present in the human genome; however, little is known about the regulation of miR transcription. Because miR levels are deregulated in chronic lymphocytic leukemia (CLL) and signal transducer and activator of transcription (STAT)-3 is constitutively activated in CLL, we sought to determine whether STAT3 affects the transcription of miR genes in CLL cells.
METHODS
We used publically available data from the ENCODE project to identify putative STAT3 binding sites in the promoters of miR genes. Then we transfected CLL cells with STAT3-shRNA or with an empty vector, and to determine which miRs are differentially expressed, we used a miR microarray approach followed by validation of the microarray results for 6 miRs using quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
We identified putative STAT3 binding sites in 160 promoter regions of 200 miRs, including miR-21, miR-29, and miR-155, whose levels have been reported to be upregulated in CLL. Levels of 72 miRs were downregulated (n = 63) or upregulated (n = 9). qRT-PCR confirmed the array data in 5 of 6 miRs.
CONCLUSIONS
The presence of activated STAT3 has a profound effect on miR expression in CLL cells.
背景
人类基因组中大约存在 1000 种 microRNAs（miRs），但miR 转录的调控机制知之甚少。由于慢性淋巴细胞白血病（CLL）中 miR 水平失调，且信号转导和转录激活因子 3（STAT-3）在 CLL 中持续激活，我们试图确定 STAT3 是否会影响 CLL 细胞中 miR 基因的转录。
方法
我们利用 ENCODE 项目中公开的可用数据，鉴定 miR 基因启动子中可能的 STAT3 结合位点。然后，我们用 STAT3-shRNA 或空载体转染 CLL 细胞，为了确定哪些 miR 表达差异，我们使用 miR 微阵列方法，然后使用定量实时聚合酶链反应（qRT-PCR）验证 6 个 miR 的微阵列结果。
结果
我们在 200 个 miR 的 160 个启动子区域中鉴定出了可能的 STAT3 结合位点，包括 miR-21、miR-29 和 miR-155，它们的水平已被报道在 CLL 中上调。72 个 miR 的水平下调（n=63）或上调（n=9）。qRT-PCR 验证了 5 个 miR 的微阵列数据。
结论
激活的 STAT3 的存在对 CLL 细胞中 miR 的表达有深远影响。
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