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

Hao Huang,Xingjiu Yang,Mengyuan Li,Kejuan Li,Ran Gao,Ruimin Zhu,Juanjuan Hu,Yong Han,Rongfei Wei,Xiaowei Zhang

doi:10.18632/oncotarget.21873

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.

Highlights

Gastric cancer (GC) is one of the most common cancers and the third cause in the global cancer-related mortality [1,2,3]
Kaplan–Meier analysis indicated that a low heterogeneous nuclear ribonucleoprotein K (HNRNPK) transcript level indicated poor overall survival (OS) and free of progression (FP) in GC patients (Figure 1A and 1B, P < 0.001 and P < 0.001)
These results indicated that a high level of the HNRNPK transcript could predict good outcomes for GC patients, and could be a candidate biomarker to evaluate the prognosis of patients in early stage

Summary

Introduction

Gastric cancer (GC) is one of the most common cancers and the third cause in the global cancer-related mortality [1,2,3]. Detection is the most promising approach to improve long-term survival of GC patients, but approximately 70% of GC patients are initially diagnosed in their late stages have missed the option of surgical resection [4]. It is important to identify new prognostic markers and therapeutic targets to improve the detection of GC in early stage and targeted treatment. Heterogeneous nuclear ribonucleoprotein K (HNRNPK), a component of the hnRNP complex, is a highly conserved RNA and DNA binding protein [7]. It contains three consecutive K homologue (KH) s, a nuclear localization signals (NLS) and a nuclear shuttling domain (KNS). HNRNPK preferentially and tenaciously binds to poly(C), and regulates transcription, translation, pre-mRNA splicing, RNA stability, chromatin remodeling, and signal transduction [11]

Methods

Results

Conclusion