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A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.

ABSTRACT: Alternative RNA splicing is an essential process to yield proteomic diversity in eukaryotic cells, and aberrant splicing is often associated with numerous human diseases and cancers. We recently described serine/arginine-rich splicing factor 3 (SRSF3 or SRp20) being a proto-oncogene. However, the SRSF3-regulated splicing events responsible for its oncogenic activities remain largely unknown. By global profiling of the SRSF3-regulated splicing events in human osteosarcoma U2OS cells, we found that SRSF3 regulates the expression of 60 genes including ERRFI1, ANXA1 and TGFB2, and 182 splicing events in 164 genes, including EP300, PUS3, CLINT1, PKP4, KIF23, CHK1, SMC2, CKLF, MAP4, MBNL1, MELK, DDX5, PABPC1, MAP4K4, Sp1 and SRSF1, which are primarily associated with cell proliferation or cell cycle. Two SRSF3-binding motifs, CCAGC(G)C and A(G)CAGCA, are enriched to the alternative exons. An SRSF3-binding site in the EP300 exon 14 is essential for exon 14 inclusion. We found that the expression of SRSF1 and SRSF3 are mutually dependent and coexpressed in normal and tumor tissues/cells. SRSF3 also significantly regulates the expression of at least 20 miRNAs, including a subset of oncogenic or tumor suppressive miRNAs. These data indicate that SRSF3 affects a global change of gene expression to maintain cell homeostasis.

SUBMITTER: Ajiro M

PROVIDER: S-EPMC4770227 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.

Ajiro Masahiko M Jia Rong R Yang Yanqin Y Zhu Jun J Zheng Zhi-Ming ZM

Nucleic acids research 20151223 4

Alternative RNA splicing is an essential process to yield proteomic diversity in eukaryotic cells, and aberrant splicing is often associated with numerous human diseases and cancers. We recently described serine/arginine-rich splicing factor 3 (SRSF3 or SRp20) being a proto-oncogene. However, the SRSF3-regulated splicing events responsible for its oncogenic activities remain largely unknown. By global profiling of the SRSF3-regulated splicing events in human osteosarcoma U2OS cells, we found tha ...[more]

PMID: 26704980

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Project description:Background: Osteosarcoma typically occurs in adolescents, and the survival rate of patients with metastatic and recurrent osteosarcoma remains low. Abnormal regulation of alternative splicing is associated with the development of osteosarcoma. However, there is no genome-wide analysis of the function and regulatory mechanisms of aberrant alternative splicing associated with osteosarcoma. Methods: Published transcriptome data on osteosarcoma (GSE126209) derived from osteosarcoma patient tissue were downloaded. Gene expression profiling by high-throughput sequencing was performed on 9 normal samples and 10 tumor samples for genome-wide identification of osteosarcoma-related alternative splicing events. The potential function of osteosarcoma-associated alternative splicing events was examined by immune infiltration and correlation analysis. Regulation of aberrantly expressed RNA-binding proteins (RBPs) related to alternative splicing in osteosarcoma was clarified by co-expression analysis. Results: A total of 63 alternative splicing events, which are highly credible and dominant, were identified. GO enrichment analysis indicated that alternative splicing may be closely related to the immune response process. Immune infiltration analysis showed significant changes in the percentages of CD8 T cells, resting memory CD4 T cells, activated memory CD4 T cells, monocytes, resting dendritic cells, and activated mast cells in tumors compared to normal tissues, indicating the involvement of these immune cell types in the occurrence of osteosarcoma. Moreover, the analysis identified alternative splicing events that were co-altered with resting memory CD4 T cells, resting dendritic cells, and activated mast cells, events that may be associated with regulation of the osteosarcoma immune microenvironment. In addition, a co-regulatory network (RBP-RAS-immune) of osteosarcoma-associated RBPs with aberrant alternative splicing and altered immune cells was established. These RBPs include NOP58, FAM120C, DYNC1H1, TRAP1, and LMNA, which may serve as molecular targets for osteosarcoma immune regulation. Conclusion: These findings allow us to further understand the causes of osteosarcoma development and provide a new research direction for osteosarcoma immunotherapy or targeted therapy.

Dataset Information

A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.

Publications

A genome landscape of SRSF3-regulated splicing events and gene expression in human osteosarcoma U2OS cells.

Similar Datasets

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