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

作者:Li, Ning; Kaur, Sippy; Greshock, Joel; Lassus, Heini; Zhong, Xiaomin; Wang, Yanling; Leminen, Arto; Shao, Zhongjun; Hu, Xiaowen; Liang, Shun; Katsaros, Dionyssios; Huang, Qihong; Butzow, Ralf; Weber, Barbara L.; Coukos, George; Zhang, Lin*
来源:Cancer Research, 2012, 72(1): 154-164.
DOI:10.1158/0008-5472.CAN-11-2484

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.