RNA结合蛋白（RBPs）的失调是癌症的一个特征。研究异常RBPs的生物功能和分子机制可帮助发现新的癌症生物标志物和治疗策略。为了确定三重阴性乳腺癌（TNBC）中的致癌RBPs，我们采用了体内CRISPR筛选和TNBC进展模型，发现小核核糖核蛋白多肽C（SNRPC）是U1小核核糖核蛋白粒子（U1 snRNP）的一个亚单位，并是TNBC进展的关键调节因子。SNRPC经常上调，与TNBC患者的预后不良相符。SNRPC减少明显损伤了TNBC细胞在体内外的增殖、迁移和侵袭。此外，SNRPC对U1 snRNP的稳定至关重要，并有助于RNA Pol II受控的转录程序。降低SNRPC可减少一些致癌基因（TNFAIP2、E2F2和CDK4）的RNA Pol II富集和降低其表达水平。此外，SNRPC的删除部分通过调节TNFAIP2-Rac1-β- 坦顿信号通路来抑制TNBC的进展。总之，这些数据表明SNRPC在TNBC中发挥致病作用，是不良预后的标志物，并可能成为不可治疗的TNBC患者的有价值的治疗靶点。

Dysregulation of RNA-binding proteins (RBPs) is one of the characteristics of cancer. Investigating the biological functions and molecular mechanisms of abnormal RBPs can help uncover new cancer biomarkers and treatment strategies. To identify oncogenic RBPs in triple-negative breast cancer (TNBC), we employed an in vivo CRISPR screen and a TNBC progression model, which revealed small nuclear ribonucleoprotein polypeptide C (SNRPC), a subunit of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), as a key modulator of TNBC progression. SNRPC was frequently upregulated, which corresponded to poor prognosis in TNBC patients. SNRPC ablation significantly impaired the proliferation, migration and invasion of TNBC cells in vitro and in vivo. In addition, SNRPC was essential for the stability of U1 snRNP and contributed to the RNA Pol II-controlled transcriptional program. Knockdown of SNRPC decreased RNA Pol II enrichment on a subset of oncogenes (TNFAIP2, E2F2 and CDK4) and reduced their expression levels. Furthermore, SNRPC deletion was confirmed to inhibit TNBC progression partially through regulation of the TNFAIP2-Rac1-β-catenin signaling pathway. Taken together, this data suggests that SNRPC plays an oncogenic role in TNBC, is a marker of poor prognosis, and may be a valuable therapeutic target for patients with intractable TNBC.