Down regulation of G protein-coupled receptor 137 expression inhibits proliferation and promotes apoptosis in leukemia cells

Li-Jie Men,Ya-Ping Wu,Hai-Ying Chen,Jing-Xia Wang,Ji-Zhu Liu,Tai-Wu Xiao,Shuang-Feng Chen,Li Zhang,Guang-Yao Li

doi:10.1186/s12935-018-0507-1

Abstract

BackgroundG protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment.Materials and methodsIn this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined.ResultsThere was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60.ConclusionsThe expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia.

Highlights

G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, can be hijacked by tumor cells
The expression of G protein-coupled receptors 137 (GPR137) is associated with the proliferation of leukemia cell lines
As demonstrated by western blot analysis (Fig. 2c, d), GPR137 was constitutively expressed in both cell lines, which indicates that it may be associated with tumorgenesis

Summary

Introduction

G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. G-protein-coupled receptors (GPRs) comprise the largest family of cell-surface molecules. They are the crucial players in multiple physiological functions by promoting cell connection through recognition of diverse ligands, like amines, bioactive peptides, nucleosides and lipids, which modulate various signaling pathways [12]. By proliferating independently, escaping the immune system, increasing their blood supply, invading their surrounding tissues and propagating to other organs [13], cancer cells can hijack the normal physiological functions of GPRs and participate in tumor growth and metastasis. Many GPRs-mediated reactions are not dependent on a single biochemical route, but rely on a complicated network of transduction cascades which include many physiological activities and tumor development [14]

Methods

Results

Discussion

Conclusion