Endocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer, yet long-term treatment often causes acquired resistance, which results in recurrence and metastasis. Recent studies have revealed that RNA-binding proteins (RBP) are involved in tumorigenesis. Here, we demonstrate that PSF/SFPQ is an RBP that potentially predicts poor prognosis of patients with ER-positive breast cancer by posttranscriptionally regulating ERα ( ESR1 ) mRNA expression. Strong PSF immunoreactivity correlated with shorter overall survival in patients with ER-positive breast cancer. PSF was predominantly expressed in a model of tamoxifen-resistant breast cancer cells, and depletion of PSF attenuated proliferation of cultured cells and xenografted tumors. PSF expression was significantly associated with estrogen signaling. PSF siRNA downregulated ESR1 mRNA by inhibiting nuclear export of the RNA. Integrative analyses of microarray and RNA immunoprecipitation sequencing also identified SCFD2, TRA2B , and ASPM as targets of PSF. Among the PSF targets, SCFD2 was a poor prognostic indicator of breast cancer and SCFD2 knockdown significantly suppressed breast cancer cell proliferation. Collectively, this study shows that PSF plays a pathophysiologic role in ER-positive breast cancer by posttranscriptionally regulating expression of its target genes such as ESR1 and SCFD2 . Overall, PSF and SCFD2 could be potential diagnostic and therapeutic targets for primary and hormone-refractory breast cancers. Significance: This study defines oncogenic roles of RNA-binding protein PSF, which exhibits posttranscriptional regulation in ER-positive breast cancer.

中文翻译：

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PSF 通过 ESR1 和 SCFD2 的转录后调节促进 ER 阳性乳腺癌进展。

内分泌治疗是雌激素受体（ER）阳性乳腺癌的标准治疗方法，但长期治疗往往会导致获得性耐药，从而导致复发和转移。最近的研究表明，RNA 结合蛋白 (RBP) 与肿瘤发生有关。在这里，我们证明 PSF/SFPQ 是一种 RBP，可通过转录后调节 ERα (ESR1) mRNA 表达来潜在地预测 ER 阳性乳腺癌患者的不良预后。在 ER 阳性乳腺癌患者中，强 PSF 免疫反应性与较短的总生存期相关。PSF 主要在他莫昔芬抗性乳腺癌细胞模型中表达，并且 PSF 的消耗减弱了培养细胞和异种移植肿瘤的增殖。PSF 表达与雌激素信号显着相关。PSF siRNA 通过抑制 RNA 的核输出来下调 ESR1 mRNA。微阵列和 RNA 免疫沉淀测序的综合分析也将 SCFD2、TRA2B 和 ASPM 确定为 PSF 的靶点。在 PSF 目标中，SCFD2 是乳腺癌的不良预后指标，并且 SCFD2 敲低显着抑制了乳腺癌细胞增殖。总的来说，这项研究表明 PSF 通过转录后调节其靶基因（如 ESR1 和 SCFD2）的表达，在 ER 阳性乳腺癌中发挥病理生理作用。总体而言，PSF 和 SCFD2 可能成为原发性和激素难治性乳腺癌的潜在诊断和治疗靶点。意义：本研究定义了 RNA 结合蛋白 PSF 的致癌作用，该蛋白在 ER 阳性乳腺癌中表现出转录后调控。