EBV Conference 2008 Guangzhou - Baylor College of Medicine

181 (RegID: 1706; 1785)
Ziming Du
Institution: Sun Yat-Sen University Cancer Center and Department of Microbiolgy, Tumor and Cell
Biology, Karolinska Institutet
e-mail: ziming.du@ki.se
EPSTEIN-BARR VIRUS ENCODED LATENT MEMBRANE PROTEIN 1 AND 2A INDUCED
MICRORNA-155 EXPRESSION IN NASOPHARYNGEAL CARCINOMA
Zi-Ming Du1,2*, Li-fu Hu1, Jian-Yong Shao2*, Ingemar Ernberg1
Posterabstract:
MicroRNAs (miRNAs) are a new class of non-coding RNAs , which can exert their gene regulatory
activity by specific mRNA degradation or translational inhibition. The objectives of this project are to
shed light on the contribution of miRNAs in EBV oncogenesis in NPC and to explore if they can be used
as molecular markers for diagnosis and prognosis prediction to improve the clinical handling of NPC
patients.
Differential expressed miRNAs and mRNAs regulated by LMP1 and LMP2A were investigated by
screens with miRNAs microarray and Affymetrix Gene Chip in NPC TW03 cells respectively. Quantitive
Realtime PCR was used to validate these array data. Compared with vector control, miR-155 expression
were increased in two LMP1-CNE1 stable clones (158.24 ± 25.23 fold; 168.89±30.87 fold), one
LMP1-TW03 stable clone (42.56 ± 9.87 fold), and in one LMP2A-TW03 stable clones (2.16 ± 0.41 fold).
With TFSEARCH NF-kB and AP-1 binding site were found in the promoter region of pri-miR155 (BIC).
For targets prediction of miR-155, four algorithms - miRanda (John et al., 2004), TargetScan (Lewis et al.,
2005), PicTar (Krek et al., 2005) and miRBase (Enright et al., 2003) were used and we chose 47 common
putative targets which were in at least 3 algorithms. Combined with the mRNAs array data, we found that
BACH1, CARHSP1, HIVEP2, JMJD1A, TLE4, FGF7, USP48 and FBX011, which are putative targets of
miR-155, were downregulated by LMP1 and LMP2A in TW03 cells.
The functional significance of selected miRNAs will be verified by switching on or off their expression
using mimic or anti-sense of miR-155 followed by assessement of their targets and biological effects.
Finally, we will use in situ hybridization (ISH) or immunohistochemistry (IHC) to detect the expression of
selected miRNAs and their targets in NPC biopsy and evaluate the diagnostic and prognostic predictive
value.
EBV Conference 2008 Guangzhou
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