Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J.
Over-expression of miR-100 is responsible for the low-expression of ATM in the human glioma cell line: M059J.
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DOI：
10.1016/j.dnarep.2010.08.007
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发表时间：
2010-11-10
期刊：
影响因子：
3.8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Ng WL;Yan D;Zhang X;Mo YY;Wang Y
M059 J和M059 K细胞分离自同一人类恶性胶质瘤的不同部分。M059 J细胞由于缺乏DNA-PKcs和ATM的低表达而比M059 K细胞更敏感。M059 J中DNA-PKcs缺失的机制是由于PRKDC（DNA-PKcs基因）的移码突变;然而，ATM在M059 J细胞中低表达的原因尚不清楚。我们发现M059 J细胞中ATM水平较低的主要原因与转录调控或蛋白降解无关，而是与转录后调控有关。基于数据库信息，我们发现ATM的3 '-非翻译区（UTR）含有miR-100结合位点。通过RNA酶保护试验和qRT-PCR，我们鉴定了miR-100在M059 J细胞中的高表达。我们进一步证明了miR-100与ATM的3 '-UTR结合。敲低miR-100促进M059 J细胞中ATM表达在M059 K细胞和其他癌细胞中上调miR-100降低ATM表达并使这些细胞对电离辐射敏感。这些结果表明ATM是miR-100的靶点，说明ATM在M059 J细胞中的低表达主要是由于miR-100的高表达。这些结果也表明，miR-100可能是一个有用的工具，以靶向ATM和致敏肿瘤细胞电离辐射。
M059J and M059K cells were isolated from different portions of the same human malignant glioma. M059J cells are more radiosensitive than M059K cells due to the absence of DNA-PKcs and low-expression of ATM. The mechanism concerning the absence of DNA-PKcs in M059J is due to the frameshift mutation in PRKDC (DNA-PKcs gene); however, the reason for the low expression of ATM in M059J cells remains unclear. We showed here that the main reason for the lower ATM level in M059J cells was not related to the transcriptional regulation or protein degradation but was related to post-transcriptional regulation. Based on database information, we found that the 3’-untranslational region (UTR) of ATM contains a miR-100-binding site. By using an RNase protection assay and qRT-PCR, we identified that miR-100 is highly-expressed in M059J cells. We further demonstrated that miR-100 bound to the 3’-UTR of ATM. Knocking-down miR-100 promotes ATM expression in M059J cells. Up-regulating miR-100 in M059K cells and other cancer cells reduces ATM expression and sensitizes these cells to ionizing radiation. These results indicate that ATM is a target of miR-100, elucidating that the low-expression of ATM in M059J cells is mainly due to the high-expression of miR-100. These results also suggest that miR-100 could be a useful tool to target ATM and sensitize tumor cells to ionizing radiation.
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影响因子：
11.2
作者：
Peng, YL;Woods, RG;Bedford, JS
通讯作者：
Bedford, JS
影响因子：
4.8
作者：
Dalby, B;Cates, S;Ciccarone, VC
通讯作者：
Ciccarone, VC
影响因子：
3.3
作者：
Gately, DP;Hittle, JC;Yen, TJ
通讯作者：
Yen, TJ
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan
影响因子：
3.7
作者：
Yan D;Ng WL;Zhang X;Wang P;Zhang Z;Mo YY;Mao H;Hao C;Olson JJ;Curran WJ;Wang Y
通讯作者：
Wang Y