Forced expression of DYRK2 exerts anti-tumor effects via apoptotic induction in liver cancer

• Published in: Cancer letters Vol. 451; pp. 100 - 109
• Main Authors: Yokoyama-Mashima, Shiho, Yogosawa, Satomi, Kanegae, Yumi, Hirooka, Shinichi, Yoshida, Saishu, Horiuchi, Takashi, Ohashi, Toya, Yanaga, Katsuhiko, Saruta, Masayuki, Oikawa, Tsunekazu, Yoshida, Kiyotsugu
• Format: Journal Article
• Language: English; Japanese
• Published: Ireland Elsevier B.V 01.06.2019; Elsevier Limited
• Subjects: Adenoviridae - genetics; Adenovirus; Adenoviruses; Animals; Apoptosis; Breast cancer; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell survival; Down-Regulation; Dyrk Kinases; DYRK2; Gene therapy; Genomes; Hepatocytes; Heterografts; Humans; Kinases; Laboratories; Liver; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Medical prognosis; Mice; Prognosis; Proliferation; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proteins; Survival; Survival Analysis; Tumor suppressor genes; Tumors; Tyrosine; Liver cancer; DYRK2; Proliferation; Adenovirus; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2019.02.046

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. •DYRK 2 suppresses tumor growth ability of liver cancer.•Adenovirus-mediated overexpression of DYRK2 induces apoptosis in tumor.•Liver cancer patients with low DYRK2 expression have shorter overall survival.