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

Abstract

Osteosarcoma is a malignant bone tumor characterized by high metastatic potential and recurrence rates after therapy. The small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB), core components of a spliceosome, exhibit up-regulation across several cancer types. However, the precise role of SNRPB in osteosarcoma progression remains poorly elucidated. Herein, SNRPB expression was explored in human osteosarcoma tissues and normal bone tissues by immunohistochemical staining, revealing a notable up-regulation of SNRPB in osteosarcoma, correlating with diminished survival rates. 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 human umbilical vascular endothelial cells, while enhancing osteosarcoma cell apoptosis. Mechanistically, SNRPB promoted the transcription of ribonucleotide reductase subunit M2 via E2F transcription factor 1. Further rescue experiments indicated that ribonucleotide reductase subunit M2 was required for SNRPB-induced malignant behaviors in osteosarcoma. Additionally, the function of SNRPB in osteosarcoma cell growth and apoptosis was confirmed to be associated with ataxia-telangiectasia mutated (ATM) signaling pathway activation. In conclusion, these findings provide initial insights into the underlying mechanisms governing SNRPB-induced osteosarcoma progression, and we propose SNRPB as a novel therapeutic target in osteosarcoma management.