Wang Feifei, Wang Lin, Pan Jihong
Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
Mol Med Rep. 2015 Jan;11(1):698-704. doi: 10.3892/mmr.2014.2691. Epub 2014 Oct 17.
PACE4 is one of the proprotein convertases (PC) that participate in the post-translational activation of inactive proteins, leading to mature, biologically active proteins. The processing reactions occur in pairs of basic amino acids. PACE4 is an extracellular PC that binds to growth factors and several components of the extracellular matrix contributing to tumor progression. In the present study, the PACE4 gene was silenced by small interfering RNA (siRNA), and the knockdown human breast cancer MDA-MB-231 cells showed significantly reduced proliferation, migration and invasion rates. Flow cytometry analysis indicated that downregulation of PACE4 increases the percentage of cells arrested at the G0/G1 phase. Moreover, the expression of genes involved in cell growth, invasion and adhesion, i.e., IGF-2, MMP9 and MPZL2 was significantly decreased following siRNA-mediated silencing of PACE4. Taken together, these results indicate that PACE4 plays an important role in human breast cancer, and that it might represent a novel target for breast cancer therapy.
PACE4是前体蛋白转化酶（PC）之一，参与无活性蛋白的翻译后激活，生成成熟的、具有生物活性的蛋白。加工反应发生在成对的碱性氨基酸处。PACE4是一种细胞外PC，它与生长因子和细胞外基质的几种成分结合，促进肿瘤进展。在本研究中，小干扰RNA（siRNA）使PACE4基因沉默，敲低后的人乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭率显著降低。流式细胞术分析表明，PACE4的下调增加了停滞在G0/G1期的细胞百分比。此外，在siRNA介导的PACE4沉默后，参与细胞生长、侵袭和黏附的基因，即IGF-2、MMP9和MPZL2的表达显著降低。综上所述，这些结果表明PACE4在人类乳腺癌中起重要作用，可能是乳腺癌治疗的一个新靶点。
