Small Nuclear Ribonucleoprotein Polypeptides B and B1 Promote Osteosarcoma Progression via Activating the ATM Signaling Pathway through Ribonucleotide Reductase Subunit M2

Abstract

Osteosarcoma is a malignant bone tumor characterized by high metastatic potential and recurrence rates post-therapy. The small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB), a core component of spliceosome, have been reported to exhibit upregulation across several cancer types. However, the precise role of SNRPB in osteosarcoma progression remains poorly elucidated. Herein, we explored SNRPB expression in human osteosarcoma tissues and normal bone tissues by immunohistochemical staining (IHC) staining, revealing a notable upregulation of SNRPB in osteosarcoma, correlating with diminished survival rates. Moreover, the in vitro loss-of-function experiments showed that SNRPB knockdown significantly suppressed the osteosarcoma cell proliferation and migration, as well as tubule formation of HUVECs, while enhancing osteosarcoma cell apoptosis. Mechanistically, we revealed that SNRPB promoted the transcription of ribonucleotide reductase subunit M2 (RRM2) via E2F transcription factor 1 (E2F1). Further rescue experiments indicated that RRM2 was required for SNRPB-induced malignant behaviors in osteosarcoma. Additionally, we confirmed that the function of SNRPB in osteosarcoma cell growth and apoptosis was associated with ATM signaling pathway activation. In conclusion, our findings provide initial insights into the underlying mechanisms governing SNRPB-induced osteosarcoma progression and proposed for SNRPB as a novel therapeutic target in osteosarcoma management.