Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro.

Qingmin Chen,Yahui Liu,Ludong Tan,Ze Zhang,Zhe Jin

doi:10.1155/2020/3098327

Abstract

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

Highlights

Hepatocellular carcinoma (HCC) is one of the most malignant cancers that occurred in liver [1]
To preliminarily investigate the relationship between Cellular retinoic acid-binding protein 2 (CRABP2) expression and HCC, first, we employed immunohistochemistry and western blotting to detect the expression of CRABP2 in HCC tissues
These results indicate that the effects of CRABP2 on the survival, proliferation, invasion of HCC cells may be involved in the regulation of the Extracellular signal-regulated kinases (ERK)-vascular endothelial growth factor (VEGF) pathway

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most malignant cancers that occurred in liver [1]. It is urgent to develop new therapies and identify novel therapeutic targets for HCC. RAR by binding RA response element of target gene to regulate gene expression, CRABP2 is able to regulate cell proliferation, apoptosis, and metastasis by transporting retinoic acid to the nucleus [8,9,10]. It has been widely reported that abnormal CRABP2 expression change is associated with oncogenesis [11, 12]. Feng et al reported that CRABP2 can suppress invasion and metastasis of ER+ breast cancer by regulating the stability of Lats in vitro and in vivo [14]. Few is known about the effects of CRABP2 in HCC

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