蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究

doi:10.19401/j.cnki.1007-3639.2020.04.004

中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (4): 261-267.doi: 10.19401/j.cnki.1007-3639.2020.04.004

蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究

蒙秋华，田　婧，覃　妍，蒙秋晓，董　敏

广西医科大学药学院，广西南宁 530021

出版日期:2020-04-30 发布日期:2020-05-11
通信作者: 董　敏 E-mail: dongmin0217@sina.com
基金资助:
国家自然科学基金（81302859）；广西壮族自治区高校科学技术项目（2013YB053）；广西壮族自治区自然科学基金（2018GXNSFAA050121）；大学生创新创业课题（201910598311）。

The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway

MENG Qiuhua, TIAN Jing, QIN Yan, MENG Qiuxiao, DONG Min

School of Pharmacy, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Published:2020-04-30 Online:2020-05-11
Contact: DONG Min E-mail: dongmin0217@sina.com

摘要/Abstract

摘要： 背景与目的：蛋白酪氨酸磷酸酶受体D（protein tyrosine phosphatase receptor type delta，PTPRD）和程序性死亡［蛋白］配体-1（programmed death ligand-1，PD-L1）在肝癌组织的异常表达与肿瘤侵袭和转移有关。信号转导与转录激活因子3（signal transducer and activator of transcription-3，STAT3）通路在癌症中起着关键作用，影响免疫系统的许多方面，STAT3异常激活与PTPRD和PD-L1的异常表达密切相关，然而PTPRD和PD-L1的相关性目前鲜见文献报道。探讨PTPRD和PD-L1在肝癌组织中的表达相关性，进一步在肝癌细胞中观察PTPRD是否可调控PD-L1。方法：采用免疫组织化学法分析2018年10月—2019年1月广西医科大学附属肿瘤医院肝二病区收治的原发性肝癌并经手术治疗的16例肝癌患者的肿瘤标本及其癌旁标本中PTPRD和PD-L的蛋白水平，采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）检测同一标本PTPRD和PD-L1 mRNA的表达，分析两者的相关性。采用蛋白质印迹法（Western blot）检测过表达或沉默PTPRD对PD-L1、STAT3和p-STAT3蛋白水平的影响。采用RTFQ-PCR检测PTPRD过表达对PD-L1转录水平的影响。结果：肝癌组织中PTPRD的表达显著低于癌旁组织（P＜0.05），PD-L1表达显著高于癌旁组织（P＜0.05），两者表达呈负相关性（r ² =0.275 8，P=0.036 7）；PTPRD过表达时，PD-L1、STAT3和p-STAT3蛋白的表达水平下降（P＜0.05）,PTPRD沉默时，PD-L1的表达增高。 结论：PTPRD和PD-L1表达水平在肝癌中呈负相关，PTPRD可能通过STAT3信号通路调节PD-L1的表达。PTPRD有望成为肝癌免疫治疗新靶点。

关键词: 蛋白酪氨酸磷酸酶D, 程序性死亡［蛋白］配体1, 信号转导与转录激活因子信号通路, 肝细胞癌

Abstract: Background and purpose: The aberrant expressions of protein tyrosine phosphatase receptor type delta (PTPRD) and programmed death ligand 1 (PD-L1) in hepatocellular carcinoma are related to tumor invasion and metastasis. It is well recognized that signal transducer and activator of transcription-3 (STAT3) plays a critical role in cancer. It also affects many aspects of the immune system. Aberrant activation of STAT3 is closely related to the abnormal expressions of PTPRD and PD-L1. However, until now, few reports demonstrated the correlation between PTPRD and PD-L1. This study aimed to investigate the expressions and correlation of PTPRD and PD-L1 and whether PTPRD regulates PD-L1 in hepatocellular carcinoma tissues, and draw out the underlying mechanisms in this process. Methods: Expression levels of PD-L1 and PTPRD in hepatocellular carcinoma tissues from 16 patients with hepatocellular carcinoma receiving surgery in Guangxi Medical University during Oct. 2018 to Jan. 2019 were detected by immunochemistry and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and their relationship was analyzed. The effects of overexpression or knockdown of PTPRD on PD-L1, STAT3 and p-STAT3 protein expressions were detected by Western blot, and PD-L1 mRNA expression was detected by RTFQ-PCR. Results: The expression of PTPRD was significantly lower in hepatocellular carcinoma tissues than in adjacent tissues (P<0.05), while the expression of PD-L1 was significantly higher (P<0.05).There was a negative correlation between PTPRD and PD-L1 expressions in hepatocellular carcinoma (r ²=0.275 8, P=0.036 7). The protein expressions of PD-L1, STAT3 and p-STAT3 were down-regulated when PTPRD was overexpressed (P<0.05), while the expression level of PD-L1was increased in tissues with PTPRD knockdown (P<0.05). Conclusion: PTPRD and PD-L1 are negatively correlated in hepatocellular carcinoma. PTPRD regulates PD-L1 expression through the STAT3 pathway, and it is expected to become a new target for the immunotherapy of hepatocellular carcinoma.

Key words: Protein tyrosine phosphatase receptor type delta, Programmed death ligand-1, Signal transducer and activator of transcription pathway, Hepatocellular carcinoma

蒙秋华, 田　婧, 覃　妍, 蒙秋晓, 董　敏. 蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究[J]. 中国癌症杂志, 2020, 30(4): 261-267.

MENG Qiuhua, TIAN Jing, QIN Yan, MENG Qiuxiao, DONG Min. The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway[J]. China Oncology, 2020, 30(4): 261-267.

[1]	肖　锋, 肖静文, 邵建国, 陈丽燕, 顾春燕 . PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性[J]. 中国癌症杂志, 2021, 31(5): 419-427.
[2]	牛　娜, 林岩松 . ⁹⁰ Y微球选择性内放射治疗在肝细胞癌中的应用及研究进展[J]. 中国癌症杂志, 2021, 31(5): 428-434.
[3]	刘　敏, 陈添亮, 郭　娟, 伊雪, 高洪泉, 巫佳翠, 王玉孝 . 蛋白激酶CβⅡ通过IL-6自分泌途径促进肝细胞癌侵袭的研究[J]. 中国癌症杂志, 2021, 31(4): 268-276.
[4]	章　俊, 董宇华, 杨　叶, 张梦琪, 何　常 . Regorafenib联合TAS102新策略治疗肝细胞癌的研究[J]. 中国癌症杂志, 2021, 31(4): 294-301.
[5]	张　欣, 周　成, 周恺乾, 柏乾明, 蒋冬先, 宿杰阿克苏, 侯英勇, 王　征, 纪　元 . 肉瘤样肝细胞癌中MET基因扩增与预后的相关性分析[J]. 中国癌症杂志, 2020, 30(9): 641-649.
[6]	徐珊珊 , 宋琴琴 , 仵红娇 , 付　宁 , 车玲玉 , 金　敏 , 刘　冲 , 韩素桂 , 张雪梅 , 张　志 . 膜辅助蛋白CD46 rs1970530遗传变异对肝癌发病风险的影响[J]. 中国癌症杂志, 2020, 30(9): 656-660.
[7]	皮思蝶, 郑小川, 毛彬力, 崔　静, 胡　源. SAMHD1通过调控p27表达抑制肝细胞癌细胞增殖的研究[J]. 中国癌症杂志, 2020, 30(7): 489-496.
[8]	虞　梅,梅　琪,韩莹莹,翟凌云,沙红芳,徐祥勇,倪　娟,崔建巍,丁　红 . 超声造影灌注时相分析在监控肝硬化结节演变和恶变中的临床价值[J]. 中国癌症杂志, 2019, 29(9): 709-714.
[9]	马家强，曹春梅，Shyamal Goswami,陈　沁，高　强，张晓明. 肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究[J]. 中国癌症杂志, 2019, 29(5): 352-361.
[10]	彭雪强,杨　良,张小东,等. 自噬相关基因5在肝癌组织中的表达及临床意义[J]. 中国癌症杂志, 2018, 28(5): 321-326.
[11]	武明辉,谭红娜,吴青霞,等. 肝脏磁共振T2WI图像纹理特征预测肝细胞癌患者微血管侵犯的价值[J]. 中国癌症杂志, 2018, 28(3): 191-196.
[12]	肖金成,康鑫鑫,白淇文,等. 经肝动脉化疗栓塞联合射频消融治疗原发性肝细胞癌合并门静脉癌栓的预后影响因素分析[J]. 中国癌症杂志, 2018, 28(3): 222-228.
[13]	王秀月,赵　川,陈　彻,等. 长链非编码RNA作为肝细胞癌诊断新型血清标志物的meta分析[J]. 中国癌症杂志, 2018, 28(3): 229-235.
[14]	肖锋,顾春燕,钱　铮,等. 精氨酸酶2表达与肝细胞癌增殖凋亡及预后的关系研究[J]. 中国癌症杂志, 2018, 28(2): 105-110.
[15]	许文芳,费迎明,周建康,等. XB130基因对肝细胞癌细胞增殖的影响及其机制[J]. 中国癌症杂志, 2018, 28(2): 117-122.

蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究

The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价