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A Combined Array-Based Comparative Genomic Hybridization and Functional Library Screening Approach Identifies mir-30d As an Oncomir in Cancer

  作者 Li, N; Kaur, S; Greshock, J; Lassus, H; Zhong, XM; Wang, YL; Leminen, A; Shao, ZJ; Hu, XW; Liang, S; Katsaros, D; Huang, QH; Butzow, R; Weber, BL; Coukos, G; Zhang, L  
  选自 期刊  Cancer research;  卷期  2012年72-1;  页码  154-164  
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[摘要]Oncomirs are microRNAs (miRNA) that acts as oncogenes or tumor suppressor genes. Efficient identification of oncomirs remains a challenge. Here we report a novel, clinically guided genetic screening approach for the identification of oncomirs, identifying mir-30d through this strategy. mir-30d regulates tumor cell proliferation, apoptosis, senescence, and migration. The chromosomal locus harboring mir-30d was amplified in more than 30% of multiple types of human solid tumors (n=1,283). Importantly, higher levels of mir-30d expression were associated significantly with poor clinical outcomes in ovarian cancer patients (n-330, P-0.0016). Mechanistic investigations suggested that mir-30d regulates a large number of cancer-associated genes, including the apoptotic caspase CASP3. The guided genetic screening approach validated by this study offers a powerful tool to identify oncomirs that may have utility as biomarkers or targets for drug development. Cancer Res; 72(1); 154-64. (C) 2011 AACR.

 
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