RNaseH2A is involved in human gliomagenesis through the regulation of cell proliferation and apoptosis.

Mutations in the RNaseH2A gene are involved in Aicardi‑Goutieres syndrome, an autosomal recessive neurological dysfunction; however, studies assessing RNaseH2A in relation to glioma are scarce. This study aimed to assess the role of RNaseH2A in glioma and to unveil the underlying mechanisms. RNaseH2A was silenced in glioblastoma cell lines U87 and U251. Gene expression was assessed in the cells transfected with RNaseH2A shRNA or scramble shRNA by microarrays, validated by quantitative real time PCR. Protein expression was evaluated by western blot analysis. Cell proliferation was assessed by the MTT assay; cell cycle distribution and apoptosis were analyzed by flow cytometry. Finally, the effects of RNaseH2A on colony formation and tumorigenicity were assessed in vitro and in a mouse xenograft model, respectively. RNaseH2A was successively knocked down in U87 and U251 cells. Notably, RNaseH2A silencing resulted in impaired cell proliferation, with 70.7 and 57.8% reduction in the U87 and U251 cells, respectively, with the cell cycle being blocked in the G0/G1 phase in vitro. Meanwhile, clone formation was significantly reduced by RNaseH2A knockdown, which also increased cell apoptosis by approximately 4.5-fold. In nude mice, tumor size was significantly decreased after RNaseH2A knockdown: 219.29±246.43 vs. 1160.26±222.61 mm3 for the control group; similar findings were obtained for tumor weight (0.261±0.245 and 1.127±0.232 g) in the shRNA and control groups, respectively). In the microarray data, RNaseH2A was shown to modulate several signaling pathways responsible for cell proliferation and apoptosis, such as IL-6 and FAS pathways. RNaseH2A may be involved in human gliomagenesis, likely by regulating signaling pathways responsible for cell proliferation and apoptosis.