An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells.
An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells.
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DOI：
10.1186/1476-4598-10-135
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发表时间：
2011-11-03
期刊：
影响因子：
37.3
通讯作者：
Ochiya T
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Yoshioka Y;Minoura K;Takahashi RU;Takeshita F;Taya T;Horii R;Fukuoka Y;Kato T;Kosaka N;Ochiya T
Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance. Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR. These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.
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影响因子：
56.9
作者：
Mayr, Christine;Hemann, Michael T.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.1073/pnas.0703942104
发表时间：
2007-10-09
影响因子：
11.1
作者：
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82.9
作者：
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11.2
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通讯作者：
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影响因子：
20.3
作者：
Sampath, Deepa;Calin, George A.;Plunkett, William
通讯作者：
Plunkett, William