Abstract 235: SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma

Abstract

Abstract Background Gliomblastoma (GBM) is associated with disproportionately high morbidity and mortality, reflecting the need to develop new diagnostic and therapeutic targets for this disease. Recently, accumulating evidence has suggested that small nucleolar RNAs (snoRNAs) are gaining prominence and are more actively involved in tumorigenesis than previously thought. However, no report concerning the implication of snoRNAs in glioma has been published to date. Methods The expression of SNORD76 and its host gene, GAS5, in glioma patients were evaluated by quantitative PCR. Flow cytometry was used to analyze to cell cycle distribution after SNORD76 over-expression. After SNORD76 over-expression in GBM cell lines, cell growth and anti-tumor effect were investigated in vitro and in vivo. Results SNORD76 expression was selectively decreased in glioblastoma (WHO grade IV) compared with low grades glioma (WHO grade II and III). Forcibly expressed SNORD76 inhibited proliferation and anchorage-independent growth of glioma cells. Flow cytometry demonstrated that enforced SNORD76 expression arrested the cells at S phase of the cell cycle. Western blot Cell cycle-associated proteins cyclin A1, cyclin B1 and p107 were down-regulated after SNORD76 over-expression, while the expression of Rb and pRb increased. The growth of orthotopic tumors was significantly inhibited by forced expression of SNORD76. Conclusion In summary, engineered restoration of SNORD76 caused marked repression of glioma growth in vitro and in vivo. The tumor suppression could be achieved at least partially through inducing S phase arrest in an Rb-associated manner. Thus, SNORD76 may act as a potential tumor suppressive gene in the development and progression of glioblastoma and may be a potential specific glioblastoma biomarker. Citation Format: Luyue chen, Lei Han, kailiang zhang, jianwei wei, peiyu pu, jianning zhang, chunsheng kang. SNORD76, a box C/D snoRNA, acts as a tumor suppressor in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 235. doi:10.1158/1538-7445.AM2015-235