Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Sci. 2022 Nov;113(11):3801-3813. doi: 10.1111/cas.15430. Epub 2022 Sep 6.
RNA binding proteins (RBPs) play pivotal roles in breast cancer (BC) development. As an RBP, Processing of precursor 7 (POP7) is one of the subunits of RNase P and RNase MRP, however, its exact function and mechanism in BC remain unknown. Here, we showed that expression of POP7 was frequently increased in BC cells and in primary breast tumors. Upregulated POP7 significantly promoted BC cell proliferation in vitro and primary tumor growth in vivo. POP7 also increased cell migration, invasion in vitro, and lung metastasis in vivo. Through RNA immunoprecipitation coupled with sequencing (RIP-seq), we found that POP7 bound preferentially to intron regions and POP7-binding peak associated genes were mainly enriched in cancer-related pathways. Furthermore, POP7 regulated Interleukin Enhancer Binding Factor 3 (ILF3) expression through influencing its mRNA stability. Knockdown of ILF3 significantly impaired the increased malignant potential of POP7-overexpressing cells, suggesting that POP7 enhances BC progression through regulating ILF3 expression. Collectively, our findings provide the first evidence for the important role of POP7 and its regulation of ILF3 in promoting BC progression.
RNA 结合蛋白 (RBPs) 在乳腺癌 (BC) 的发展中起着关键作用。作为 RBP，前体加工蛋白 7 (POP7) 是 RNase P 和 RNase MRP 的亚基之一，但其在 BC 中的确切功能和机制尚不清楚。在这里，我们表明 POP7 的表达在 BC 细胞和原发性乳腺癌肿瘤中经常增加。上调的 POP7 显著促进了 BC 细胞在体外的增殖和体内原发性肿瘤的生长。POP7 还增加了细胞迁移、侵袭的体外能力，并增加了体内的肺转移。通过 RNA 免疫沉淀结合测序 (RIP-seq)，我们发现 POP7 优先结合内含子区域，POP7 结合峰相关基因主要富集在癌症相关途径中。此外，POP7 通过影响其 mRNA 稳定性来调节白细胞介素增强因子 3 (ILF3) 的表达。ILF3 的敲低显著削弱了过表达 POP7 的细胞恶性潜能的增加，表明 POP7 通过调节 ILF3 的表达来增强 BC 的进展。总之，我们的研究结果为 POP7 及其调节 ILF3 促进 BC 进展的重要作用提供了第一个证据。
