Pygo2 siRNA Inhibit the Growth and Increase Apoptosis of U251 Cell by Suppressing Histone H3K4 Trimethylation
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The development of novel therapeutic strategies for glioma requires the identification of molecular targets involved in malignancy. Pygopus (Pygo) is a new discovered and specific downstream component of canonical Wnt signaling. Our previous study has demonstrated that Pygo2 is highly expressed in and promotes the growth of glioma cells. However, the role of Pygo2 in glioma remains to be elucidated. In the current study, we investigated the role of Pygo2 in human glioma U251 cells and showed that knocking down of the expression of Pygo2 in U251 cells using lentivirally expressed siRNA have inhibited cell proliferation and increased apoptosis through decreasing H3K4me3 expression. Moreover, we found Pygo2 was enriched in U251 glioma cancer stem-like cells and Pygo2 siRNA resulted in a reduced number as well as size of tumor spheres. According to our result, this paper now links mechanistically Pygo2’s role in histone modification to its enhancement/reduction of proliferation/apoptosis in glioma cells and indicate that Pygo2 may play an important role in self-renew and proliferation in U251 glioma cancer stem-like cells.
KeywordsPygo2 Growth Apoptosis H3K4me3
Central nervous system
Lymphoid-enhancing factor 1/T-cell factor
Trimethylation of histone H3 at lysine 4
Epidermal growth factor
Basic fibroblast growth factor
Green fluorescent protein
Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
This work was supported by the National Natural Science Foundation of China (no. 81271332) and Fujiani Natural Science Foundation (2009D002).
Conflict of Interest
All the authors of this study declare no conflict of interest.
- Chen J, Luo Q, Yuan Y, Huang X, Cai W, Li C, Wei T, Zhang L, Yang M, Liu Q, Ye G, Dai X, Li B (2010) Pygo2 associates with MLL2 histone methyltransferase and GCN5 histone acetyltransferase complexes to augment Wnt target gene expression and breast cancer stem-like cell expansion. Mol Cell Biol 30:5621–5635. doi: 10.1128/MCB.00465-10 PubMedCentralPubMedCrossRefGoogle Scholar
- Gu B, Sun P, Yuan Y, Moraes RC, Li A, Teng A, Agrawal A, Rheaume C, Bilanchone V, Veltmaat JM, Takemaru K, Millar S, Lee EY, Lewis MT, Li B, Dai X (2009) Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol 185:811–826. doi: 10.1083/jcb.200810133 PubMedCentralPubMedCrossRefGoogle Scholar
- Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. doi: 10.1016/S1470-2045(09)70025-7 PubMedCrossRefGoogle Scholar