EBV Conference 2008 Guangzhou - Baylor College of Medicine

180 (RegID: 1601; 1602)
Hua-Chien Chen
Institution: Chang Gung University
e-mail: hcchen@mail.cgu.edu.tw
PROFILING AND PATHWAY ANALYSIS OF MICRORNAS ALTERED IN NASOPHARYNGEAL
CARCINOMA
HC Chen, GH Chen, YH Chen, WL Liao, CY Liu, KP Chang, YS Chang and SJ Chen
Posterabstract:
MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20-23 nucleotides in
length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop
real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal
carcinoma sample (NPC) and 9 adjacent non-tumor tissue (NT) and identified several miRNAs whose
expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs,
including miR-17-92 cluster and miR-155, are among the miRNAs up-regulated in NPC. Tumor
suppressor miRNAs, including miR-34 family, miR-143, and miR-145, were significantly down-regulated
in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational
analysis was performed to predict the pathways collectively targeted by the 22 most significantly
down-regulated miRNAs.
Several biological pathways and networks that are well-characterized in cancer were significantly targeted
by the down-regulated microRNAs. These pathways include Wnt pathways, growth factor regulated G1-S
cell cycle progression, VEGF signaling pathways. The expression levels of several genes involved in G1-S
progression, cyclin D2, cyclin E2, CDC25A, were inversely correlated with the levels of down-regulated
microRNAs in NPC tissues. We examined the microRNA binding sites on the 3’UTR of cyclin E2 and
found conserved binding sites for miR-34c, miR-200a, and miR-9. Expression levels of cyclin E2 in NPC
tissue show significant inverse correlation with these three microRNAs. These results indicate that these
down-regulated miRNAs coordinately regulate several oncogenic pathways and provide a experimentally
testable hypothesis regarding collective regulatory function of microRNAs in cancer.
EBV Conference 2008 Guangzhou
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