Abstract
Osteosarcoma (OS) is the most common malignant bone tumor, characterized by a high propensity for metastasis. Recent studies have highlighted the role of alternative splicing in cancer metastasis, although the precise mechanisms underlying aberrant splicing in OS invasion and metastasis remain unclear. Here, we analyzed consistently differentially expressed genes and differentially alternative splicing events between primary and metastatic OS to identify potential genes associated with OS progression. U1 small nuclear ribonucleoprotein 70K (SNRNP70) emerged as both differentially expressed and spliced, with elevated SNRNP70 levels correlating with poor prognosis in pateints with OS. Functional experiments demonstrated that SNRNP70 overexpression enhanced the proliferation and metastasis of OS cells in vitro, while its depletion reduced these capabilities in vivo. Mechanistically, SNRNP70 directly interacted with CD55, modulating its alternative splicing and promoting tumor progression in OS. Additionally, metastatic OS samples exhibited increased infiltration of resting immune cells, and single-cell RNA sequencing revealed communication between SNRNP70-expressing osteoblastic cells and macrophages via the ADGRE5/CD55 signaling pathway. Overall, our results showed that SNRNP70 knockdown inhibited OS progression, which was associated with the splicing of CD55, indicating SNRNP70 as a promising target for OS treatment.
Authors
Wenyue Li, Linzhu Wang, Wen Tian, Weihang Ji, Danyang Bing, Yan Wang, Bingqian Xu, Jiayue Feng, Peng Zhang, Haihai Liang, Yunyan Gu, Baofeng Yang
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