期刊
CANCER RESEARCH
卷 72, 期 1, 页码 154-164出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-11-2484
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资金
- Department of Defense [W81XWH-10-1-0082]
- NIH [R01CA142776]
- Ovarian Cancer SPORE [P50-CA83638-7951]
- Ovarian Cancer Research Fund Tilberis Scholar Award
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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