Human tumor microRNA signatures derived from large-scale oligonucleotide microarray datasets.

摘要

The expression profiles of microRNAs (miRNAs) are associated with the initiation and progression of human tumors. DNA microarrays are widely used to explore the expression patterns of miRNAs. Because of the limited sample size and experimental expense, the statistical power of individual research projects is not sufficient to yield a robust conclusion. However, collected microarray datasets of expression profiles provide opportunities to compile the information of individual studies. Our study carried out a comprehensive meta-analysis of miRNA expression microarray datasets from 28 published tumor studies; it comprises 33 comparisons and nearly 4,000 tumor and corresponding nontumorous samples. This work reports 52 miRNAs as common signatures that are dysregulated in tumors. In addition to the commonly altered miRNAs, five solid cancers displayed specific tissue patterns of altered miRNAs as well. The meta-analysis also revealed some novel tumor-related miRNAs such as hsa-miR-144, hsa-miR-130b, hsa-miR-132, hsa-miR-154, hsa-miR-192 and hsa-miR-345. We further validated the expression pattern of hsa-miR-154 in human hepatocellular carcinoma by RT-PCR. Restoration of intracellular miR-154 inhibited tumor cell malignance and the G(1)/S transition in cancer cells. Both bioinformatic prediction and western blotting demonstrated that miR-154 could target CCND2. In addition, expression patterns of miR-154 were inversely correlated with those of CCND2 in hepatocellular carcinoma. Overall, this study used a large-scale data analysis to identify a qualified list of miRNAs that are consistently changed in tumors, which could lead to a better understanding of human tumor etiology.