Investigation into the role of small nucleolar RNA U44 in leukaemia

Abstract

Small nucleolar RNAs (snoRNAs) are a class of small non-coding RNAs that act as guide RNAs for post-transcriptional chemical modifications of ribosomal and spliceosome RNAs. Recent independent reports have indicated that these small non-coding RNAs are involved in the control of cell fate and their dysfunction or dysregulation of their expression might be associated with oncogenesis. SNORD44 is a C/D box small nucleolar RNA that has been reported to show decreased expression levels in breast cancer and head and neck squamous cell carcinoma tissues. The SNORD44 host gene is the long non-coding RNA growth arrest specific transcript 5 (GAS5), which has been strongly implicated in various types of cancers. Expression of SNORD44 has been reported to be decreased in breast cancer cells along with leukemic T-cells. However, the function of SNORD44 in the regulation of leukemic cell fate is still unknown. In this study, the effects of SNORD44 overexpression have been investigated in two leukemic T-cell lines, Jurkat and CEM-C7. Overexpression of SNORD44 caused a reduction in the number of viable and total cell count and an increase in basal apoptosis. Mutations in SNORD44 abolished the growth inhibitory and proapoptotic effects of SNORD44, suggesting that the structure of SNORD44 is important to perform its effects. Treating the cells with the pan-caspase inhibitor Z-VAD-FMK also inhibited SNORD44 growth inhibitory effects, implicating caspases in SNORD44 mechanisms of action. Overall the data showed that SNORD44 has tumour suppressing effects on leukemic T-cells. From these findings we postulate that control of survival and apoptosis by SNORD44 has significant consequences for leukaemia pathogenesis.