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

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 regul...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2012-01, Vol.72 (1), p.154-164
Main Authors: NING LI, KAUR, Sippy, KATSAROS, Dionyssios, QIHONG HUANG, BÜTZOW, Ralf, WEBER, Barbara L, COUKOS, George, LIN ZHANG, GRESHOCK, Joel, LASSUS, Heini, XIAOMIN ZHONG, YANLING WANG, LEMINEN, Arto, ZHONGJUN SHAO, XIAOWEN HU, SHUN LIANG
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Apoptosis
Apoptosis - genetics
Biological and medical sciences
biomarkers
Caspase
Cell migration
Cell Proliferation
Chromosome Mapping
Comparative Genomic Hybridization
Drug development
Female
Genetic screening
genomics
Humans
In Situ Hybridization
Medical sciences
Mice
MicroRNAs - genetics
miRNA
Oncogenes
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Pharmacology. Drug treatments
Polymorphism, Single Nucleotide
Real-Time Polymerase Chain Reaction
Senescence
Solid tumors
Tumor cells
Tumor suppressor genes
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-11-2484