Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells.
Overexpression of dicer as a result of reduced let-7 MicroRNA levels contributes to increased cell proliferation of oral cancer cells.
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DOI：
10.1002/gcc.20765
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发表时间：
2010-06
影响因子：
3.7
通讯作者：
Chan, Edward K. L.
中科院分区：
文献类型：
--
作者：
Jakymiw, Andrew;Patel, Rushi S.;Deming, Natasha;Bhattacharyya, Indraneel;Shah, Priya;Lamont, Richard J.;Stewart, Carol M.;Cohen, Donald M.;Chan, Edward K. L.
最近的报道表明，Dicer，一种微小RNA（miRNA）成熟所需的RNase III内切核酸酶，在不同类型的癌症中异常表达。此外，据报道，Dicer受let-7家族的miRNA基因调控。我们假设Dicer在口腔癌细胞中异常表达是由于let-7表达的改变，并且Dicer有助于疾病的发展和进展。在四个头颈部鳞状细胞癌（HNSCC）细胞系（包括两个口腔癌细胞系）中Dicer蛋白水平的蛋白质印迹检测表明，与正常人原代牙龈上皮细胞相比，Dicer具有4至24倍的高表达水平。此外，间接免疫荧光分析的六个口腔癌组织中有五个与正常牙龈上皮组织相比，Dicer蛋白表达增加。发现Dicer mRNA水平与HNSCC细胞系中的蛋白表达没有很好的相关性，表明Dicer蛋白表达是转录后调节的。通过实时PCR对HNSCC细胞系中let-7a和let-7 b水平的分析表明，与对照细胞相比，HNSCC细胞系中let-7 b而非let-7a显著降低。最后，早在转染后三天，用化学合成的let-7 b和靶向Dicer的小干扰RNA转染口腔癌细胞分别显著抑制细胞增殖高达83%和> 100%。总之，这些数据表明，口腔癌细胞中Dicer表达水平的升高与let-7 b的下调和细胞增殖的增加相关。
Recent reports have demonstrated that Dicer, an RNase III endonuclease required for microRNA (miRNA) maturation, is aberrantly expressed in different types of cancer. Furthermore, Dicer has been reported to be regulated by the let-7 family of miRNA genes. We hypothesize that Dicer is aberrantly expressed in oral cancer cells due to altered expressions of let-7, and that Dicer contributes to the development and progression of the disease. Western blot examination of Dicer protein levels in four head and neck squamous cell carcinoma (HNSCC) cell lines, including two oral cancer cell lines, demonstrated that Dicer had between 4 to 24 fold higher expression levels when compared to normal human primary gingival epithelial cells. Furthermore, five of six oral cancer tissues analyzed by indirect immunofluorescence had increased Dicer protein expression, compared to normal gingival epithelial tissue. The Dicer mRNA levels were not found to correlate well with protein expression in the HNSCC cell lines, suggesting that Dicer protein expression was post-transcriptionally regulated. Analysis of let-7a and let-7b levels in HNSCC cell lines by real-time PCR demonstrated that let-7b, but not let-7a, was significantly reduced in the HNSCC cell lines compared to control cells. Lastly, transfection of oral cancer cells with chemically synthesized let-7b and small interfering RNAs targeting Dicer significantly inhibited cell proliferation up to 83% and >100%, respectively, as early as three days post-transfection. Together, these data demonstrate that elevated expression levels of Dicer in oral cancer cells correlate with down-regulation of let-7b and increased cell proliferation.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
21.3
作者：
Jakymiw, A;Lian, SL;Chan, EKL
通讯作者：
Chan, EKL
影响因子：
6.4
作者：
Chang, Steven S.;Jiang, Wei Wen;Smith, Ian;Poeta, Luana M.;Begum, Shahnaz;Glazer, Chad;Shan, Shannon;Westra, William;Sidransky, David;Califano, Joseph A.
通讯作者：
Califano, Joseph A.
影响因子：
4
作者：
Jakymiw, Andrew;Pauley, Kaleb M.;Chan, Edward K. L.
通讯作者：
Chan, Edward K. L.
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.