蛋白酪氨酸磷酸酶受体R型对胶质瘤细胞恶性生物学行为的影响

doi:10.11958/20240831

天津医药 ›› 2025, Vol. 53 ›› Issue (1): 9-13.doi: 10.11958/20240831

蛋白酪氨酸磷酸酶受体R型对胶质瘤细胞恶性生物学行为的影响

高蕊¹(), 周官恩¹, 洪雁¹, 颜艳²^,³^,^△()

1 天津市环湖医院神经内科（邮编300350）
2 天津医科大学神经内外科及神经康复科临床学院
3 天津市环湖医院检验科

收稿日期:2024-07-08 修回日期:2024-10-21 出版日期:2025-01-15 发布日期:2025-02-06
通讯作者: ^△E-mail：yanyandoctor1982@163.com
作者简介:高蕊（1986），女，主治医师，主要从事神经肿瘤及神经免疫学方面研究。E-mail：gaorui3721@126.com
基金资助:
国家自然科学基金资助项目(81972349)

Effect of protein tyrosine phosphatase receptor R-type on malignant biological behavior of glioma cells

GAO Rui¹(), ZHOU Guanen¹, HONG Yan¹, YAN Yan²^,³^,^△()

1 Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300350, China
2 Clinical College of Neurology, Neurosurgery and Department of Neurological Rehabilitation, Tianjin Medical University
3 Department of Clinical Laboratory, Tianjin Huanhu Hospital

Received:2024-07-08 Revised:2024-10-21 Published:2025-01-15 Online:2025-02-06
Contact: ^△E-mail：yanyandoctor1982@163.com

高蕊, 周官恩, 洪雁, 颜艳. 蛋白酪氨酸磷酸酶受体R型对胶质瘤细胞恶性生物学行为的影响[J]. 天津医药, 2025, 53(1): 9-13.

GAO Rui, ZHOU Guanen, HONG Yan, YAN Yan. Effect of protein tyrosine phosphatase receptor R-type on malignant biological behavior of glioma cells[J]. Tianjin Medical Journal, 2025, 53(1): 9-13.

摘要/Abstract

摘要：

目的探索蛋白酪氨酸磷酸酶受体R型（PTPRR）对胶质瘤细胞恶性生物学行为的影响。方法应用UALCAN网站对癌症基因组图谱（TCGA）数据库中胶质瘤样本PTPRR的表达情况进行分析。取20例胶质瘤患者术中切除的新鲜脑胶质瘤组织及20例创伤性脑出血患者的正常脑组织，培养人胶质瘤细胞株及人星形胶质细胞系，取U87细胞分别转染PTPRR的过表达质粒pcDNA3.1/PTPRR（pcDNA3.1/PTPRR组）和空白对照质粒pcDNA3.1（pcDNA3.1组）。实时定量聚合酶链反应（qRT-PCR）检测胶质瘤细胞系及胶质瘤组织的PTPRR mRNA表达；CCK-8实验检测细胞活性；集落形成实验检测细胞增殖能力；Transwell实验检测细胞迁移及侵袭能力；并进行细胞凋亡实验。结果 UALCAN网站分析显示胶质瘤中PTPRR mRNA表达水平低于正常脑组织，且高级别胶质瘤低于低级别胶质瘤；PTPRR低/中表达者的生存期较高表达者更短。qRT-PCR结果显示，PTPRR mRNA在胶质瘤细胞系及胶质瘤组织中均呈低表达；CCK-8实验结果显示，过表达PTPRR后24 h、48 h的胶质瘤细胞活性较pcDNA3.1组均降低。集落形成实验、Transwell迁移及侵袭实验结果显示，过表达PTPRR后胶质瘤细胞集落形成个数、迁移及侵袭能力较pcDNA3.1组均降低。细胞凋亡实验结果显示，过表达PTPRR后胶质瘤细胞凋亡率升高。结论 PTPRR在胶质瘤中呈低表达，且作为抑癌基因抑制胶质瘤细胞的活性、增殖、迁移及侵袭能力，促进胶质瘤细胞凋亡。

关键词: 神经胶质瘤, 细胞增殖, 细胞运动, 肿瘤浸润, 蛋白酪氨酸磷酸酶受体R型

Abstract:

Objective To explore effects of protein tyrosine phosphatase receptor type R (PTPRR) on malignant biological behavior of glioma cells.Methods UALCAN website was used to analyze the expression of PTPRR in glioma samples from the Cancer Genome Atlas (TCGA) database. The fresh brain glioma tissue samples of 20 patients with glioma and normal brain tissue samples of 20 patients with traumatic cerebral hemorrhage removed during operation were obtained. Human glioma cell line and human astrocyte cell line were cultured. U87 cells were respectively transfected with PTPRR over-expression plasmid pcDNA3.1/PTPRR (pcDNA3.1/PTPRR group) and blank control plasmid pcDNA3.1 (pcDNA3.1 group). The expression of PTPRR mRNA in different glioma cell lines and glioma tissue samples were detected by quantitative real-time PCR. Cell activity was detected by CCK-8 assay. Cell proliferation capacity was detected by colony formation assay. Cell migration and invasion ability were detected by transwell assay. Meanwhile, the cell apoptosis experiment was performed.Results The result of UALCAN database analysis indicated that the expression of PTPRR in glioma was lower than that in normal brain tissue, and the expression of PTPRR was lower in high grade gliomas than that of low grade gliomas. The survival time of glioma patients with low/medium PTPRR expression was shorter than that of patients with high PTPRR expression. The result quantitative real-time PCR showed that the expression levels of PTPRR mRNA in different glioma cell lines and glioma tissue were decreased. CCK-8 assay showed that the cell viability at 24 h and 48 h after over-expression of PTPRR was decreased respectively compared with the pcDNA3.1 group. Results of colony formation assay, Transwell migration and invasion assays showed that the number of colony formation, migration and invasion ability of glioma cells after over-expression of PTPRR were lower than the pcDNA3.1 group. The result of apoptosis experiment showed that the apoptosis rate of glioma cells after over-expression of PTPRR was increased compared with that of the pcDNA3.1 group.Conclusion The expression of PTPRR in glioma is lower. PTPRR acted as a tumor suppressor gene inhibits the activity, proliferation, migration and invasion of glioma cells, and promotes glioma cell apoptosis.

Key words: glioma, cell proliferation, cell movement, neoplasm invasiveness, protein tyrosine phosphatase receptor type R

中图分类号:

R739.41

图/表 7

表1 引物序列

Tab.1 Primer sequence

基因名称	引物序列（5′→3′）	产物大小/bp
PTPRR	上游：ACTGTCCGAGGCAAAGAC 下游：CAGAGGTAGCGGTGGTAG	125
β-actin	上游：CGTGACATTAAGGAGAAGCTG 下游：CTAGAAGCATTTGCGGTGGAC	501

图1 UALCAN网站分析PTPRR在胶质瘤中的表达情况 A：多形性胶质母细胞瘤与正常脑组织中PTPRR的表达差异；TPM：Transcrip Per Million；B：高级别胶质瘤（Ⅲ级）与低级别胶质瘤（Ⅱ级）中PTPRR的表达差异；C：PTPRR表达对低级别胶质瘤患者生存期的影响；D：PTPRR表达和肿瘤分级（Ⅱ级、Ⅲ级）对胶质瘤患者生存期的影响；a：高表达+Ⅱ级(n=72)；b：高表达+Ⅲ级(n=56)；c：低/中表达+Ⅱ级(n=173)；d：低/中表达+Ⅲ级(n=56)。

Fig.1 UALCAN website used to analyze the expression of PTPRR in glioma

表2 2组PTPRR mRNA表达、细胞活性和细胞增殖能力比较

Tab.2 Comparison of PTPRR mRNA expression, cell activity and cell proliferation ability between the two groups （n=3，$\bar{x}$±s）

组别	PTPRR mRNA	细胞活性/OD值			细胞集落数/个
组别	PTPRR mRNA	0 h	24 h	48 h	细胞集落数/个
pcDNA3.1组	1.00±0.23	1.00±0.02	1.00±0.02	1.00±0.01	91.33±6.55
pcDNA3.1/PTPRR组	34.77±3.22	0.97±0.02	0.81±0.02	0.74±0.06	24.00±2.94
t	14.900^＊	0.672	11.520^＊	12.660^＊	12.340^＊

图2 集落形成实验检测PTPRR对胶质瘤细胞增殖的影响

Fig.2 Effects of PTPRR on the cell proliferation of glioma cells investigated by colony formation assays

表3 过表达PTPRR后细胞迁移和侵袭能力的比较

Tab.3 Comparison of cell migration and invasion after over-expression of PTPRR （n=3，$\bar{x}$±s）

组别	迁移数/（个/视野）	侵袭数/（个/视野）
pcDNA3.1组	116.00±3.74	77.67±4.99
pcDNA3.1/PTPRR组	78.00±3.27	41.33±2.87
t	7.703^＊	12.760^＊

图3 Transwell实验检测PTPRR对胶质瘤细胞迁移及侵袭能力的影响

Fig.3 Effects of PTPRR on the migration and invasion of glioma cells investigated by Transwell assays

图4 细胞凋亡实验检测PTPRR对胶质瘤细胞凋亡的影响

Fig.4 The effect of PTPRR on apoptosis of glioma cells detected by apoptosis experiment

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蛋白酪氨酸磷酸酶受体R型对胶质瘤细胞恶性生物学行为的影响

Effect of protein tyrosine phosphatase receptor R-type on malignant biological behavior of glioma cells

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