PARP1通过调节RNF144A抑制乳腺癌细胞凋亡

doi:10.19401/j.cnki.1007-3639.2019.04.003

中国癌症杂志 ›› 2019, Vol. 29 ›› Issue (4): 257-264.doi: 10.19401/j.cnki.1007-3639.2019.04.003

PARP1通过调节RNF144A抑制乳腺癌细胞凋亡

曹金玲¹，张烨¹，张方淋²，李大强^1，2

1. 复旦大学上海医学院生物医学研究院，上海 200032 ；
2. 复旦大学肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032

出版日期:2019-04-30 发布日期:2019-05-17
通信作者: 李大强 E-mail：daqiangli1974@fudan.edu.cn

PARP1 inhibits apoptosis of breast cancer cells by regulating RNF144A

CAO Jinling¹, ZHANG Ye¹, ZHANG Fanglin², LI Daqiang^1,2

1. Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Cancer Institute of Fudan University, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Published:2019-04-30 Online:2019-05-17
Contact: LI Daqiang E-mail: daqiangli1974@fudan.edu.cn

摘要/Abstract

摘要： 背景与目的：乳腺癌是全球女性最常见的恶性肿瘤，但其发病机制尚不清楚。我们前期研究发现环指蛋白144A（ring finger protein 144A，RNF144A）调节多聚ADP核糖聚合酶1［poly（ADP ribose）polymerase 1，PARP1］的稳定性，进而影响乳腺癌细胞对PARP抑制剂olaparib的敏感性。该研究旨在探讨PARP1是否对RNF144A具有调节作用及其对乳腺癌细胞凋亡的影响。方法：利用免疫组织化学方法检测乳腺癌组织中PARP1的表达水平，并分析PARP1表达水平与乳腺癌患者预后的关系。采用蛋白质印迹法（Western blot）检测过表达或者敲低PARP1对RNF144A蛋白水平的影响。采用实时荧光定量聚合酶链反应（real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR）检测敲低PARP1对RNF144A转录水平的影响。利用AnnexinⅤ-PE/7-AAD双染法流式细胞术检测细胞凋亡。结果：在乳腺癌组织中PARP1表达阳性率为68%，且高表达PARP1的患者预后较差。在敲低或过表达PARP1的HEK-293T和乳腺癌细胞中，RNF144A在mRNA水平无明显变化，但其蛋白水平与PARP1表达呈负相关。Olaparib诱导细胞凋亡时，过表达PARP1细胞凋亡率较低，在过表达PARP1的细胞中重新过表达RNF144A后凋亡率有一定程度的恢复。结论：PARP1在乳腺癌细胞的表达水平与乳腺癌患者的预后相关，可能在乳腺癌的发生、发展中扮演着癌基因的角色。PARP1调节RNF144A的蛋白水平但不影响其mRNA水平。PARP1可能通过负向调节RNF144A抑制乳腺癌细胞凋亡。

关键词: 乳腺癌, 多聚ADP核糖聚合酶1, 预后, 环指蛋白144A, 凋亡

Abstract: Background and purpose: Breast cancer is the most commonly diagnosed cancer, but its underlying mechanism remains elusive. The previous studies have demonstrated that ring finger protein 144A (RNF144A) regulates the stablity of poly (ADPribose) polymerase 1 (PARP1) and thus affects the sensitivity of breast cancer cells to PARP inhibitor olaparib. This study was designed to investigate whether PARP1 could regulate RNF144A and its effect on apoptosis of breast cancer cells following treatment with olaparib. Methods: Expression levels of PARP1 in breast cancer tissues were detected by immunohistochemistry, and the relationship between PARP1 expression levels and prognosis of breast cancer patients was analyzed. The effects of overexpression or knockdown of PARP1 on RNF144A protein and mRNA expression were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR), respectively. Annexin Ⅴ-PE/7-AAD double staining was used to detect apoptosis by flow cytometry. Results: The positive rate of PARP1 expression was 68% in normal breast tissues, and patients with high expression of PARP1 had poor prognosis. Modulation of PARP1 negatively regulated RNF144A at the protein but not mRNA level. Overexpression of PARP1 enhanced anti-apoptotic effect of cells following olaparib treatment. Moreover, introduction of RNF144A in PARP1 overexpressing cells rescued the anti-apoptotic effects of PARP1 overexpression in breast cancer cells following olaparib treatment. Conclusion: The expression levels of PARP1 are associated with the prognosis of breast cancer patients, and PARP1 may play an oncogenic role in the development and progression of breast cancer. PARP1 negatively regulates RNF144A at the protein level without affecting its transcription. PARP1 inhibits apoptosis of breast cancer cells partially through regulating RNF144A.

Key words: Breast cancer, PARP1, Prognosis, RNF144A, Apoptosis

曹金玲，张烨，张方淋，李大强. PARP1通过调节RNF144A抑制乳腺癌细胞凋亡[J]. 中国癌症杂志, 2019, 29(4): 257-264.

CAO Jinling, ZHANG Ye, ZHANG Fanglin, LI Daqiang. PARP1 inhibits apoptosis of breast cancer cells by regulating RNF144A[J]. China Oncology, 2019, 29(4): 257-264.

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PARP1通过调节RNF144A抑制乳腺癌细胞凋亡

PARP1 inhibits apoptosis of breast cancer cells by regulating RNF144A

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