HNRNP A1 Promotes Lung Cancer Cell Proliferation by Modulating VRK1 Translation

International Journal of Molecular Sciences

HyeGuk Ryu¹  Kyong-Tai Kim¹  Namgyu Lee²  Do-Yeon Kim³  Kyung-Ha Lee⁴  Youngseob Jung⁵  Ji-Young Seo⁵  SungWook Kim⁵ 

[1] Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea;Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01065, USA;Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea;Division of Cosmetic Science and Technology, Daegu Haany University, Gyeongsan 38610, Korea;Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea;

关键词: HNRNP A1;    VRK1;    lung cancer;    post-transcriptional regulation;    3′UTR;   

DOI  :  10.3390/ijms22115506

来源: DOAJ

【 摘 要 】

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3′ untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element–binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3′UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.

【 授权许可】

Unknown