MicroRNA Expression Abnormalities in Pituitary Adenomas Are Associated with Distinctive Pathologic Features and May Contribute to Tumorigenesis
ZR Qian, T Tanahashi, K Yoshimoto, S Yamada, S Katsuura, EL Wang, K Rokutan, T Sano. Institute of Health Biosciences, University of Tokushima, Tokushima, Japan; Toranomon Hospital, Tokyo, Japan
Background: MicroRNAs are small noncoding RNAs that regulate gene expression by targeting specific mRNAs for degradation or translation inhibition. Recent evidence indicates that microRNAs can contribute to tumorigenesis and tumor progression and may have diagnostic and prognostic value in several human malignancies. We investigated the global microRNA expression patterns in normal human pituitary and adenomas to evaluate their involvement in tumorigenesis and clinicopathologic features of these tumor types.
Design: Using the most new miRNA microarray, we studied about 700 microRNA expression in 5 human adenohypophyses and 53 pituitary adenomas, including 11 somatotroph, 6 lactotroph, 13 corticotroph (8 associated with Cushing's disease and 5 silent), 12 gonadotroph adenomas, 2 TSHomas, 8 Null cell adenomas and 1 familial isolated pituitary adenoma. Real-time RT-PCR analysis was done to evaluate the expression of some miRNA. Web-based computer programs were used to predict potential miRNA-target gene. Pituitary tumor cell lines has been used to examine the relation between miRNAs and target genes.
Results: Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pituitary tissues: Forty-seven miRNA were differentially expressed between normal pituitary and pituitary adenomas. 32 were up-regulated and 15 down-regulated in adenomas compared to normal pituitaries. In addition, some microRNAs expression can distinguish among each tumor type. Moreover, several of the identified miRNAs are involved in tumor invasion and tumor size. Furthermore, we identified several miRNA targeted genes that may related to pituitary tumorigenesis and tumor cell proliferation in vitro.
Conclusions: These results suggest that alteration in microRNA expression and target genes is related to pituitary tumorigenesis and tumor progression. Some of them may prove useful in distinguishing tumors with different clinical behavior and may to be possible therapeutic targets for the treatment.
Monday, March 22, 2010 8:45 AM
Platform Session: Section H 1, Monday Morning