Research Paper Volume 11, Issue 18 pp 7473—7491
HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis
- 1 Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
- 2 School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China
- 3 Center of Evidence-based Medicine, Fudan University, Shanghai, China
Received: July 20, 2019 Accepted: September 2, 2019 Published: September 16, 2019
https://doi.org/10.18632/aging.102254How to Cite
Copyright © 2019 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Gastric cancer (GC) is a common disease globally with high mortality rate. It is therefore necessary to develop novel therapies targeting specific events in the pathogenesis of GC. Some hnRNP family members are involved in multiple cancer biological behaviors. However, the potential function and mechanism of hnRNPR, a new molecule of hnRNP family in GC remains unknown. We found that the expression of hnRNPR was significantly overexpressed in multiple cancers compared to the normal tissues. Functionally, hnRNPR promoted cancer cell proliferation, migration, and invasion. Knockdown of hnRNPR in two type mice models, with two types of tumors models decreased the tumor aggressiveness and metastasis. Mechanistically, hnRNPR targeted oncogenic pathways by stabilizing the expression of CCNB1 and CENPF mRNA level. Knockdown of CCNB1 and CENPF abolished the hnRNPR-induced cell growth and invasion, respectively. Furthermore, the protein level of hnRNPR in the tumor was positively correlated with the expression of CCNB1 and CENPF in clinical samples. Together, these results indicate that overexpression of hnRNPR promoted the aggressiveness of GC by increasing the mRNA expression of CCNB1 and CENPF. HnRNPR-CCNB1/CENPF axis may be a potential therapeutic target for GC treatment.
Abbreviations
HnRNPR: heterogeneous nuclear ribonucleoprotein R; TCGA: The Cancer Genome Atlas; CCK8: Cell Counting Kit-8; GSEA: Gene set enrichment analysis; IHC: Immunohistochemistry; PCR: Polymerase chain reaction; qRT–PCR: Quantitative real-time PCR; CCNB1: Cyclin B1; CENPF: Centromere Protein F.