Down‐regulation of G protein‐coupled receptor 137 by RNA interference inhibits cell growth of two hepatoma cell lines

Abstract

G protein-coupled receptors (GPCRs) are important signal transduction mediators and pharmacological therapeutic targets. G protein-coupled receptor 137 (GPR137) was initially reported as a novel orphan GPCR around 10 years ago. Some orphan GPCRs have been implicated in cancer cell proliferation and migration. The aim of this study is to investigate the role of GPR137 in hepatocellular carcinoma (HCC). GPR137 is widely expressed in several human HCC cell lines, as determined by real-time PCR. We then applied lentivirus mediated RNA interference (RNAi) to knock down GPR137 expression in two HCC cell lines HepG2 and Bel7404. Depletion of GPR137 remarkably inhibited cell proliferation and colony formation capacity. Knockdown of GPR137 in HepG2 cells led to cell cycle arrest at G0/G1 phase and G2/M phase, and induced cell apoptosis, as determined by flow cytometry analysis, which contributed to cell growth inhibition. Our findings suggested that GPR137 could facilitate HCC cell proliferation and thus promote hepatocarcinogenesis.

Emerging Roles of G Protein-Coupled Receptors in Hepatocellular Carcinoma

“…GPR137 is elevated in some human HCC cell lines. Depletion of GPR137 via lentivirus mediated RNA interference (RNAi) in HCC cell lines HepG2 and Bel7404 remarkably reduces cell viability and colony-formation ability, which increases cell apoptosis [ 82 ]. However, GPR37 expression is lower in HCC compared to the adjacent nontumorous tissues.…”

GPR137 Inhibits Cell Proliferation and Promotes Neuronal Differentiation in the Neuro2a Cells

“…GPR137 i s also known as transmembrane 7 superfamily member 1-like protein, C11orf4 or GPR137A , and is an integral membrane protein [ 3 ]. It is involved in the proliferation of tumor cells in several cancers, including ovarian [ 4 ], gastric [ 5 ], pancreatic [ 6 ], hepatoma [ 7 ], urinary/bladder [ 8 ], and prostate cancers [ 9 ], as well as medulloblastoma [ 10 ], malignant glioma [ 11 ], osteosarcoma [ 12 ], and leukemia [ 13 ]. RNA interference (RNAi)-mediated downregulation of GPR137 inhibits tumor cell growth [ 5 – 7 , 9 – 13 ].…”

“…It is involved in the proliferation of tumor cells in several cancers, including ovarian [ 4 ], gastric [ 5 ], pancreatic [ 6 ], hepatoma [ 7 ], urinary/bladder [ 8 ], and prostate cancers [ 9 ], as well as medulloblastoma [ 10 ], malignant glioma [ 11 ], osteosarcoma [ 12 ], and leukemia [ 13 ]. RNA interference (RNAi)-mediated downregulation of GPR137 inhibits tumor cell growth [ 5 – 7 , 9 – 13 ]. These results indicate that GPR137 plays a role in tumor cell proliferation and could be a potential therapeutic target for several types of cancers.…”

GPR137 promotes cell cycle exit and neuronal differentiation in the neuro2A cells

“…GPR137 is also known as transmembrane 7 superfamily member 1like protein, C11orf4 or GPR137A, and is an integral membrane protein [3]. It is involved in the proliferation of tumor cells in several cancers, including ovarian [4], gastric [5], pancreatic [6], hepatoma [7], urinary/bladder [8], and prostate cancers [9], as well as medulloblastoma [10], malignant glioma [11], osteosarcoma [12], and leukemia [13]. RNA interference (RNAi)-mediated downregulation of GPR137 inhibits tumor cell growth [5][6][7][9][10][11][12][13].…”

“…It is involved in the proliferation of tumor cells in several cancers, including ovarian [4], gastric [5], pancreatic [6], hepatoma [7], urinary/bladder [8], and prostate cancers [9], as well as medulloblastoma [10], malignant glioma [11], osteosarcoma [12], and leukemia [13]. RNA interference (RNAi)-mediated downregulation of GPR137 inhibits tumor cell growth [5][6][7][9][10][11][12][13]. These results indicate that GPR137 plays a role in tumor cell proliferation and could be a potential therapeutic target for several types of cancers.…”