Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China.
Department of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou 510800, China.
Biol Chem. 2019 Jun 26;400(7):951-963. doi: 10.1515/hsz-2018-0417.
Gelsolin (GSN) is an actin filament-capping protein that plays a key role in cell migration. Here we show that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates GSN expression level by binding to the 3'-untranslated region (3'UTR) of GSN mRNA in non-small cell lung cancers (NSCLC) H1299 cells which are highly metastatic and express high level of GSN. We found that hnRNPK overexpression increased the mRNA and protein level of GSN, whereas hnRNPK knockdown by siRNA decreased the mRNA and protein level of GSN in both H1299 and A549 cells, indicating a positive role of hnRNPK in the regulation of GSN expression. Furthermore, hnRNPK knockdown affected the migration ability of H1299 and A549 cells which could be rescued by ectopic expression of GSN in those cells. Conversely, GSN knockdown in hnRNPK-overexpressing cells could abort the stimulatory effect of hnRNPK on the cell migration. These results suggest that hnRNPK function in the regulation of cell migration is GSN-dependent. Taken together, these data unveiled a new mechanism of regulation of the GSN expression by hnRNPK and provides new clues for the discovery of new anti-metastatic therapy.
凝胶蛋白（GSN）是一种肌动蛋白丝封端蛋白，在细胞迁移中发挥关键作用。在这里，我们表明异质核核糖核蛋白 K（hnRNPK）通过与非小细胞肺癌（NSCLC）H1299 细胞中 GSN mRNA 的 3'非翻译区（3'UTR）结合来调节 GSN 的表达水平，H1299 细胞具有高转移性且表达高水平的 GSN。我们发现 hnRNPK 过表达增加了 GSN 的 mRNA 和蛋白水平，而 hnRNPK 的 siRNA 敲低降低了 H1299 和 A549 细胞中 GSN 的 mRNA 和蛋白水平，表明 hnRNPK 在 GSN 表达的调节中具有正向作用。此外，hnRNPK 的敲低影响了 H1299 和 A549 细胞的迁移能力，而在这些细胞中外源表达 GSN 可以挽救这种影响。相反，hnRNPK 过表达细胞中 GSN 的敲低可以中止 hnRNPK 对细胞迁移的刺激作用。这些结果表明 hnRNPK 在调节细胞迁移中的功能是依赖于 GSN 的。总之，这些数据揭示了 hnRNPK 调节 GSN 表达的新机制，并为发现新的抗转移治疗提供了新的线索。
