Department of Ultrasonic Medicine, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu, China.
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China.
J Cell Physiol. 2019 Aug;234(8):13629-13638. doi: 10.1002/jcp.28043. Epub 2019 Jan 4.
The discovery of cysteine-rich secretory protein 3 (CRISP3) has been made in human neutrophils for the first time. Cloning of the complementary DNA (cDNA) for CRISP3 was performed from a cDNA library of human bone marrow. In patients with mammary carcinoma, we found that lower expression of CRISP3 was connected to a significantly improved DFS (disease-free survival) and OS (overall survival). Furthermore, the CRISP3 protein level was significantly associated with negative ANXA1 protein level. In addition, the heterogeneous expression of CRISP3 had been exhibited in diverse mammary carcinoma cells. A significant higher mRNA and the protein level of CRISP3 were seen in T-47D as well as SK-BR-3 cells compared with those in other types of mammary carcinoma cells. Knockdown of CRISP3 in T-47D or SK-BR-3 cells resulted in the weakened migration or invasion abilities. Furthermore, CRISP3 knockdown significantly inhibited the ERK1/2 MAPK signaling pathway in T-47D or SK-BR-3 cells. Research results indicated that the lowering in the expression of CRISP3 is likely to serve as an unprecedented approach for the treatment of mammary carcinoma.
首次在人类中性粒细胞中发现富含半胱氨酸的分泌蛋白 3(CRISP3)。从人骨髓 cDNA 文库中克隆了 CRISP3 的 cDNA。在乳腺癌患者中,我们发现 CRISP3 的低表达与显著改善的无病生存期(DFS)和总生存期(OS)相关。此外,CRISP3 蛋白水平与阴性 ANXA1 蛋白水平显著相关。此外,CRISP3 在不同的乳腺癌细胞中表现出异质性表达。与其他类型的乳腺癌细胞相比,T-47D 和 SK-BR-3 细胞中 CRISP3 的 mRNA 和蛋白水平明显更高。在 T-47D 或 SK-BR-3 细胞中敲低 CRISP3 导致迁移或侵袭能力减弱。此外,CRISP3 敲低显著抑制了 T-47D 或 SK-BR-3 细胞中的 ERK1/2 MAPK 信号通路。研究结果表明,降低 CRISP3 的表达可能成为治疗乳腺癌的一种前所未有的方法。