SNRNP70 regulates the splicing of CD55 to promote osteosarcoma progression
Wenyue Li, Linzhu Wang, Wen Tian, Weihang Ji, Danyang Bing, Yan Wang, Bingqian Xu, Jiayue Feng, Peng Zhang, Haihai Liang, Yunyan Gu, Baofeng Yang
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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Research Article Cell biology Oncology

SNRNP70 regulates the splicing of CD55 to promote osteosarcoma progression

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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Figure 7

Metastatic OS exhibits high infiltration of quiescent immune cells.

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Metastatic OS exhibits high infiltration of quiescent immune cells. (A) ...
(A) Comparison of immune cell infiltration between primary and metastatic samples across 7 datasets. The innermost ring displays color variation according to methods, while the middle layer presents a heatmap of P values, with darker shades indicating higher significance. Red denotes cells with high infiltration proportions in metastatic samples, while blue represents cells with low infiltration proportions. Different colors represent different immune cells in the outermost layer. NK, natural killer cell; Tgd, γδ T cells; Th1; T helper 1 cells. (B) Pearson’s correlation analysis illustrating the relationship between SNRNP70 expression and infiltration proportions of M0 macrophages in GSE14359. (C) Pearson’s correlation analysis demonstrating the association between SNRNP70 expression and activities of the oxidative phosphorylation pathway in GSE14359. The x axis represents SNRNP70 expression values, while the y axis represents immune cell infiltration or metabolic pathway scores. The top depicts the distribution of expressed values, while the right illustrates the distribution of scores in 2 types. (D) Heatmap depicting metabolic pathway activities between primary and metastasis samples across 7 datasets. (E) t-SNE visualization of 91,430 cells analyzed by scRNA-seq and integrated across 9 OS samples. Clusters are annotated for cell types using canonical markers and color-coded accordingly. (F) Dot plot displaying the expression of signature genes across the 9 clusters. The size of dots represents the proportion of cells expressing the particular marker, while the spectrum of color indicates the mean expression levels of the markers. (G) Dot plot demonstrating SNRNP70 and CD55 expression in GSE152048. (H) Violin plot showing SNRNP70 expression across the 9 clusters between primary and metastatic tissues. (I) t-SNE visualization of 7 subsets of TILs. (J) Comparison of the proportions of subsets of TILs between primary and metastatic tissues. Statistical significance was calculated using a 2-tailed Wilcoxon’s rank-sum test (A and D).