TRIM59 Promotes Retinoblastoma Progression by Activating the p38–MAPK Signaling Pathway
TRIM59 Promotes Retinoblastoma Progression by Activating the p38–MAPK Signaling Pathway
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TRIM59 通过激活 p38‐MAPK 信号通路促进视网膜母细胞瘤进展
DOI：
10.1167/iovs.61.10.2
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发表时间：
2020-08
期刊：
影响因子：
--
通讯作者：
Ke Shi
中科院分区：
文献类型：
--
作者：
Chao Wu;Xue-Qin Shang;Zhi-Peng You;Qi-Fang Jin;Yu-Lan Zhang;Yue Zhou;Yue-Zhi Zhang;Ke Shi
目的视网膜母细胞瘤（Retinoblastoma，RB）是发生于儿童视网膜发育过程中的一种恶性肿瘤。本研究旨在探讨TRIM 59对视网膜母细胞瘤生长的影响及其机制。方法我们对基因表达综合数据库中的三个数据集（GSE 24673，GSE 97508和GSE 110811）进行生物信息学分析。对三种视网膜母细胞瘤细胞系进行定量逆转录PCR和免疫印迹，以验证TRIM 59作为差异表达基因。使用特异性siRNA来抑制HXO-Rb 44细胞系中的TRIM 59表达。将慢病毒载体转染到Y 79细胞系中以过表达TRIM 59。使用上述细胞系在体外探索TRIM 59对视网膜母细胞瘤细胞增殖、细胞周期和凋亡的影响。在小鼠异种移植肿瘤模型中评估TRIM 59表达对视网膜母细胞瘤细胞增殖的影响。结果TRIM 59在3株视网膜母细胞瘤细胞系中的表达均较正常对照组明显增高。TRIM 59表达下调可显著抑制HXO-Rb 44细胞的增殖和生长，促进细胞凋亡，而TRIM 59过表达可促进Y 79细胞的肿瘤进展。沉默TRIM 59还显著抑制异种移植模型中的体内肿瘤生长。机制研究显示TRIM 59上调视网膜母细胞瘤细胞中磷酸化p38、p-JNK 1/2、p-ERK 1/2和p-c-JUN的表达。值得注意的是，p38抑制剂SB 203580减弱了TRIM 59对细胞增殖、凋亡和G1/S期转变的影响。结论TRIM 59在视网膜母细胞瘤中具有致瘤作用，其促癌作用可能是通过激活p38-mitogen-activated protein kinase通路实现的。
Purpose Retinoblastoma is a malignant tumor of the developing retina that mostly occurs in children. Our study aimed to investigate the effect of tripartite motif-containing protein 59 (TRIM59) on retinoblastoma growth and the underlying mechanisms. Methods We performed bioinformatic analysis of three datasets (GSE24673, GSE97508, and GSE110811) from the Gene Expression Omnibus database. Quantitative reverse-transcription PCR and immunoblotting of three retinoblastoma cell lines were conducted to verify TRIM59 as a differentially expressed gene. Specific siRNAs were used to inhibit TRIM59 expression in the HXO-Rb44 cell line. A lentiviral vector was transfected into the Y79 cell line to overexpress TRIM59. The effects of TRIM59 on retinoblastoma cell proliferation, cell cycling, and apoptosis were explored in vitro using the abovementioned cell lines. The effect of TRIM59 expression on retinoblastoma cell proliferation was evaluated in a mouse xenograft tumor model. Results TRIM59 expression in three retinoblastoma cell lines was remarkably elevated compared with normal control. Knocking down TRIM59 expression remarkably suppressed cell proliferation and growth and promoted cell apoptosis in HXO-Rb44 cells, whereas TRIM59 overexpression promoted tumor progression in Y79 cells. Silencing TRIM59 also markedly inhibited in vivo tumor growth in the xenograft model. Mechanistic studies revealed that TRIM59 upregulated phosphorylated p38, p-JNK1/2, p-ERK1/2, and p-c-JUN expression in retinoblastoma cells. Notably, the p38 inhibitor SB203580 attenuated the effects of TRIM59 on cell proliferation, apoptosis, and the G1/S phase transition. Conclusions TRIM59 plays an oncogenic role in retinoblastoma and exerts its tumor-promotive function by activating the p38–mitogen-activated protein kinase pathway.
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