Pre-mRNA processing factor 4 (PRPF4), a core protein in U4/U6 snRNP, maintains snRNP structures by interacting with PRPF3 and cyclophilin H. Expression of the PRPF4 gene affects cell survival as well as apoptosis and is responsible for retinitis pigmentosa (RP). Proteomics analysis shows that PRPF4 may be a therapeutic target in human cancers. Nevertheless, the exact function and role of the PRPF4 gene are unclear. In this study, we assessed the expression of PRPF4 gene in human breast cancer cells. First, we confirmed that the PRPF4 gene was overexpressed in various breast cancer cell lines. Next, using breast cancer cell lines MCF7 and MDA-MB-468, we established stable cell lines with PRPF4 gene knockdown. We also performed microarray analysis to investigate molecular mechanisms underlying PRPF4 activity. All cell lines with PRPF4 gene knockdown exhibited reduced cell proliferation, remarkable reduction in anchorage-independent colony formation capacity, and reduction of PCNA protein, which is a marker cell of proliferation. Reduced expression of the PRPF4 gene induced apoptosis and changes in the expression of associated apoptotic markers in breast cancer cell lines. Knockdown of the PRPF4 gene reduced cellular capacity for migration and invasion (the key hallmarks of human cancers) and decreased the expression of genes involved in epithelial-mesenchymal transition (EMT). Microarray results showed that the expression of PPIP5K1, PPIPK2, and YWHAE genes was reduced at the transcriptional level, leading to reduced phosphorylation of p38 MAPK. These findings suggest that knockdown of PRPF4 gene slows down breast cancer progression via suppression of p38 MAPK phosphorylation. In conclusion, the PRPF4 gene plays an important role in the growth of breast cancer cells and is therefore a potential therapeutic target.

中文翻译：

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PRPF4是通过p38 MAPK信号通路影响乳腺癌细胞的生长，迁移，侵袭和凋亡而治疗乳腺癌的新型治疗靶标。

mRNA前加工因子4（PRPF4）是U4 / U6 snRNP中的核心蛋白，通过与PRPF3和亲环蛋白H相互作用来维持snRNP结构。PRPF4基因的表达影响细胞存活以及细胞凋亡，并导致色素性视网膜炎（RP） ）。蛋白质组学分析表明PRPF4可能是人类癌症的治疗靶标。但是，尚不清楚PRPF4基因的确切功能和作用。在这项研究中，我们评估了PRPF4基因在人乳腺癌细胞中的表达。首先，我们确认PRPF4基因在各种乳腺癌细胞系中过表达。接下来，我们使用乳腺癌细胞系MCF7和MDA-MB-468建立了具有PRPF4基因敲低功能的稳定细胞系。我们还进行了微阵列分析，以研究PRPF4活性的潜在分子机制。具有PRPF4基因敲低的所有细胞系均显示出降低的细胞增殖，不依赖锚定集落的形成能力显着降低以及PCNA蛋白（其是增殖的标志性细胞）降低。PRPF4基因的表达降低诱导了乳腺癌细胞株的凋亡和相关凋亡标志物表达的变化。敲低PRPF4基因会降低细胞迁移和侵袭的能力（人类癌症的主要标志），并减少上皮-间质转化（EMT）相关基因的表达。基因芯片结果显示PPIP5K1，PPIPK2和YWHAE基因的表达在转录水平上降低，从而导致p38 MAPK磷酸化降低。这些发现表明，敲低PRPF4基因可通过抑制p38 MAPK磷酸化来减慢乳腺癌的进展。总之，PRPF4基因在乳腺癌细胞的生长中起重要作用，因此是潜在的治疗靶点。