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

Oncomirs are microRNAs (miRNAs) 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 >30% of multiple types of human solid tumors (n=1,283). Importantly, 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.