CPEB4 Inhibit Cell Proliferation via Upregulating p21 mRNA Stability in Renal Cell Carcinoma

Jiehui Di,Xiaobing Qin,Zhongjun Zhao,Zhengxiang Han,Hui Wang,Guang Zhao,Yong Liu

doi:10.3389/fcell.2021.687253

Abstract

Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) has been reported to be dysregulated in a variety of cancers and seems to play paradoxical roles in different cancers. However, the functional roles of CPEB4 in Renal cell carcinoma (RCC) are still unclear. This study aims to explore the role and underlying mechanism of CPEB4 in RCC. We found that the relative expression level of CPEB4 is down-regulated in RCC tissues and cell lines, and the low CPEB4 expression is correlated with short overall and disease-free survival of RCC patients. CPEB4 significantly inhibits RCC tumor growth both in vivo and in vitro. CPEB4 exerts an anti-tumor effect by increasing p21 mRNA stability and inducing G1 cell cycle arrest in RCC. Our data revealed that CPEB4 is a tumor suppressor gene that restrains cell cycle progression upstream of p21 in RCC. These findings revealed that CPEB4 may become a promising predictive biomarker for prognosis in patients with RCC.

Highlights

Renal cell carcinoma (RCC) is the most lethal malignancies of the urinary system, and the incidence rate of RCC is continuously increasing in recent years (Yang and Chen, 2020)
To determine whether Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is involved in RCC development, we first assessed CPEB4 protein expression in 15 pairs of RCC specimens and adjacent normal tissues, its expression significantly decreased in RCC tissues compared with normal tissues (Figures 1A,B)
These results indicated that CPEB4 might be functioned as a tumor suppressor gene in RCC progression

Summary

Introduction

Renal cell carcinoma (RCC) is the most lethal malignancies of the urinary system, and the incidence rate of RCC is continuously increasing in recent years (Yang and Chen, 2020). The pathogenesis of RCC involves the alteration of varieties of intracellular gene expression (Delahunt et al, 2021). RNA binding proteins (RBPs) are involved in almost all steps of posttranscriptional regulation, whose abnormal expression are closely related to the occurrence and development of many cancers. Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a sequence-specific RBP that belongs to the CPEB family (Kurihara et al, 2003). CPEBs binds the cytoplasmic polyadenylation element (CPE; with a consensus sequence of UUUUUAU) in the 3′untranslated regions (3′-UTR) of target mRNAs to regulate mRNA stability and translation by promoting cytoplasmic polyadenylation (Ivshina et al, 2014), which mediate many biological processes including germ-cell development, cell division, cellular senescence, synaptic plasticity, and learning and memory (Richter, 2007; Chen et al, 2016)

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