The expression and significance of GPR19 gene in prostate cancer

doi:10.11958/20220419

Abstract

Abstract:

Objective To analyze the expression of G protein-coupled receptor 19 (GPR19) in prostate cancer (PCa), and explore the mechanism of GPR19 in prostate cancer. Methods TCGA and Oncomine online databases were used to analyze the expression level and clinicopathological information of GPR19 in PCa. Expression levels of GPR19 mRNA and protein in PCa cell lines were detected by qPCR and Western blot assay, and the key molecules in related pathways were verified. EdU assay was used to verify the effect of GPR19 knockdown on tumor cell proliferation. Results Database analysis showed that GPR19 gene expression was increased in PCa samples. GPR19 gene expression was related to patient's age, disease-free survival rate, Gleason score and TNM stage. Univariate Cox analysis showed that Gleason score, TNM stage and GPR19 expression were the influencing factors of progression-free survival in PCa patients. qPCR and Western blot assay showed that GPR19 was expressed higher in PCa cell lines than that of normal prostate epithelial cell line, RWPE-1. EdU experiments verified that the proliferation ability of PCa cells was reduced after GPR19 knockdown. Pathway enrichment analysis showed that GPR19 was involved in cell cycle regulation of PCa. It was confirmed that knockdown of GPR19 reduced the expression of cyclin dependent kinase 1 (CDK1), a key molecule at the G2M signaling checkpoint in PCa cells. Pathway correlation analysis showed that GPR19 had the highest correlation with CDKN3 gene. Conclusion The expression of GPR19 is increased in PCa and related to a variety of clinical information, which affects tumor cell proliferation through the G2M signaling checkpoint. GPR19 is expected to be a potential therapeutic target for PCa.

Key words: prostatic neoplasms, receptors, G-Protein-coupled, cell proliferation, cell cycle, G2 phase cell cycle checkpoints

CLC Number:

R737.25

Figures/Tables 11

References 20

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基因名称	引物序列（5′→3′）	产物大小（bp）
GPR19	上游：AAACAGACCTTCACTATGTGCTG	91
	下游：TTGCCGAAGATAGAAAACAACCA	91
CDK1	上游：CTTGGATTCTATCCCTCCTGGTCAGTAC	118
	下游：GTCAACTGGAGTTGAGTAACGAGCTGAC	118
GAPDH	上游：GGAAGGTGAAGGTCGGAGTCA	101
	下游：GTCATTGATGGCAACAATATCCACT	101

基因名称	引物序列（5′→3′）	产物大小（bp）
GPR19	上游：AAACAGACCTTCACTATGTGCTG	91
	下游：TTGCCGAAGATAGAAAACAACCA	91
CDK1	上游：CTTGGATTCTATCCCTCCTGGTCAGTAC	118
	下游：GTCAACTGGAGTTGAGTAACGAGCTGAC	118
GAPDH	上游：GGAAGGTGAAGGTCGGAGTCA	101
	下游：GTCATTGATGGCAACAATATCCACT	101

临床病理特征	n	GPR19		χ²
临床病理特征	n	高表达	低表达	χ²
总生存
存活	415	207（49.88）	208（50.12）	0.995
死亡	6	3（50.00）	3（50.00）	0.995
无进展生存
存活	369	176（47.69）	193（52.30）	5.018^＊
死亡	52	34（65.39）	18（34.62）	5.018^＊
Gleason评分
≤7分	255	109（42.75）	146（57.25）	12.460^＊
>7分	166	101（60.84）	65（39.16）	12.460^＊
TNM分期
T1~T2期	172	66（38.37）	106（61.63）	14.640^＊
T3~T4期	249	144（57.83）	105（42.17）	14.640^＊
年龄
≤60岁	192	77（40.11）	115（59.89）	12.787^＊
>60岁	229	133（58.07）	96（41.92）	12.787^＊

临床病理特征	n	GPR19		χ²
临床病理特征	n	高表达	低表达	χ²
总生存
存活	415	207（49.88）	208（50.12）	0.995
死亡	6	3（50.00）	3（50.00）	0.995
无进展生存
存活	369	176（47.69）	193（52.30）	5.018^＊
死亡	52	34（65.39）	18（34.62）	5.018^＊
Gleason评分
≤7分	255	109（42.75）	146（57.25）	12.460^＊
>7分	166	101（60.84）	65（39.16）	12.460^＊
TNM分期
T1~T2期	172	66（38.37）	106（61.63）	14.640^＊
T3~T4期	249	144（57.83）	105（42.17）	14.640^＊
年龄
≤60岁	192	77（40.11）	115（59.89）	12.787^＊
>60岁	229	133（58.07）	96（41.92）	12.787^＊

变量	β	SE	Wald χ²	P	HR	HR 95%CI
年龄	0.011	0.021	0.263	0.608	1.011	0.971~1.052
Gleason评分	0.867	0.152	32.651	<0.001	2.381	1.768~3.206
TNM分期	0.857	0.258	11.076	0.001	2.357	1.422~3.905
GPR19	0.285	0.114	6.195	0.013	1.329	1.062~1.663