Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan.
Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Cancer Lett. 2019 Jun 1;451:100-109. doi: 10.1016/j.canlet.2019.02.046. Epub 2019 Mar 6.
Liver cancer is highly aggressive and globally exhibits a poor prognosis. Therefore, the identification of novel molecules that can become targets for future therapies is urgently required. We have reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. However, the research into its clinical application as a molecular target has remained to be explored. Here we showed that DYRK2 knockdown enhanced tumor growth of liver cancer cells. Conversely and more importantly, adenovirus-mediated overexpression of DYRK2 resulted in inhibition of cell proliferation and tumor growth, and induction of apoptosis both in vitro and in vivo. Furthermore, we found that liver cancer patients with low DYRK2 expression had a significantly shorter overall survival. Given the findings that DYRK2 regulates proliferation and apoptosis of cancer cells, DYRK2 expression could be a promising predictive marker of the prognosis in liver cancer. Stabilized or forced expression of DYRK2 may become thus a potential target for novel gene therapy against liver cancer.
肝癌侵袭性强，全球预后较差。因此，迫切需要寻找新的分子作为未来治疗的靶点。我们曾报道过双特异性酪氨酸调节激酶 2（DYRK2）通过调节细胞存活、分化、增殖和凋亡发挥肿瘤抑制作用。然而，作为分子靶点的临床应用研究仍有待探索。本研究表明，敲低 DYRK2 可增强肝癌细胞的肿瘤生长。相反，更重要的是，腺病毒介导的 DYRK2 过表达可抑制细胞增殖和肿瘤生长，并诱导体外和体内的细胞凋亡。此外，我们发现低 DYRK2 表达的肝癌患者总生存期明显缩短。鉴于 DYRK2 调节癌细胞的增殖和凋亡，DYRK2 的表达可能成为肝癌预后的一个有前途的预测标志物。因此，DYRK2 的稳定或强制表达可能成为针对肝癌的新型基因治疗的潜在靶点。
