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MYC-driven U2SURP regulates alternative splicing of SAT1 to promote triple-negative breast cancer progression.
Deng, Ling; Liao, Li; Zhang, Yin-Ling; Hu, Shu-Yuan; Yang, Shao-Ying; Ma, Xiao-Yan; Huang, Min-Ying; Zhang, Fang-Lin; Li, Da-Qiang.
Afiliação
  • Deng L; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Liao L; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 2000
  • Zhang YL; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 2000
  • Hu SY; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Yang SY; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Ma XY; Department of Breast Surgery, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Huang MY; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • Zhang FL; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 2000
  • Li DQ; Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 2000
Cancer Lett ; 560: 216124, 2023 04 28.
Article em En | MEDLINE | ID: mdl-36907504
ABSTRACT
Triple-negative breast cancer (TNBC), although highly lethal, lacks validated therapeutic targets. Here, we report that U2 snRNP-associated SURP motif-containing protein (U2SURP), a poorly defined member of the serine/arginine rich protein family, was significantly upregulated in TNBC tissues, and its high expression was associated with poor prognosis of TNBC patients. MYC, a frequently amplified oncogene in TNBC tissues, enhanced U2SURP translation through an eIF3D (eukaryotic translation initiation factor 3 subunit D)-dependent mechanism, resulting in the accumulation of U2SURP in TNBC tissues. Functional assays revealed that U2SURP played an important role in facilitating tumorigenesis and metastasis of TNBC cells both in vitro and in vivo. Intriguingly, U2SURP had no significant effects on proliferative, migratory, and invasive potential of normal mammary epithelial cells. Furthermore, we found that U2SURP promoted alternative splicing of spermidine/spermine N1-acetyltransferase 1 (SAT1) pre-mRNA by removal of intron 3, resulting in an increase in the stability of SAT1 mRNA and subsequent protein expression levels. Importantly, spliced SAT1 promoted the oncogenic properties of TNBC cells, and re-expression of SAT1 in U2SURP-depleted cells partially rescued the impaired malignant phenotypes of TNBC cells caused by U2SURP knockdown both in vitro and in mice. Collectively, these findings reveal previously unknown functional and mechanism roles of the MYC-U2SURP-SAT1 signaling axis in TNBC progression and highlight U2SURP as a potential therapy target for TNBC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Acetiltransferases / Proteínas Proto-Oncogênicas c-myc / Processamento Alternativo / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ribonucleoproteínas / Acetiltransferases / Proteínas Proto-Oncogênicas c-myc / Processamento Alternativo / Neoplasias de Mama Triplo Negativas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article