HNRNPK inhibits gastric cancer cell proliferation through p53/p21/CCND1 pathway

// Hao Huang 1, * , Yong Han 2, 3, 4, * , Xingjiu Yang 1 , Mengyuan Li 1 , Ruimin Zhu 1 , Juanjuan Hu 1 , Xiaowei Zhang 5 , Rongfei Wei 1 , Kejuan Li 1 and Ran Gao 1 1 Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, P. R. China 2 Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, P. R. China 3 People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, P. R. China 4 Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou 310014, Zhejiang, P. R. China 5 Department of Gynaecology and Obstetrics, Civil Aviation General Hospital, Beijing 100123, P. R. China * These authors contributed equally to this work Correspondence to: Ran Gao, email: gaoran201708@163.com Keywords: gastric cancer (GC), HNRNPK, proliferation Received: September 05, 2017      Accepted: October 03, 2017      Published: October 17, 2017 ABSTRACT Gastric cancer (GC) is one of the most common human cancers. The molecular mechanisms underlying GC carcinogenesis and progression are still not well understood. In this study, we showed that heterogeneous nuclear ribonucleoprotein K (HNRNPK) was an effective prognostic marker for GC patients especially in early stage. Overexpression of HNRNPK can retard tumor cell proliferation and colony formation in vitro and inhibit tumor growth in vivo through p53/p21/CCND1 axis. Bioinformatics analyses indicated that HNRNPK associated genes were enriched in cell cycle and DNA replication process. Protein-protein interaction network showed that HNRNPK was physically interacted with p53, p21 and other cancer related genes. Besides, GSEA showed that HNRNPK expression was positively correlated with GAMMA radiation response and DNA repair, while negatively correlated with angiogenesis, TGF-β and Hedgehog pathway activation. Finally, several chemicals including Glycine that may repress GC progression through upregulating HNRNPK are suggested. Our study demonstrated that HNRNPK may play as a tumor suppressor in gastric cancer and could be a potential therapeutic target for GC.