Research Paper|Volume 11, Issue 18|pp 7473—7491

HnRNPR-CCNB1/CENPF axis contributes to gastric cancer proliferation and metastasis

Er-Bao Chen¹, Xuan Qin², Ke Peng¹, Qian Li¹, Cheng Tang¹, Yi-Chou Wei¹, Shan Yu¹, Lu Gan¹, Tian-Shu Liu^1,³

¹Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
²School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China
³Center of Evidence-based Medicine, Fudan University, Shanghai, China

* Equal contribution

Received: July 20, 2019Accepted: September 2, 2019Published: September 16, 2019

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.