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Invest Ophthalmol Vis Sci. 2020 Aug 3;61(10):2. doi: 10.1167/iovs.61.10.2.
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.
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.
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.
TRIM59 plays an oncogenic role in retinoblastoma and exerts its tumor-promotive function by activating the p38-mitogen-activated protein kinase pathway.
视网膜母细胞瘤是一种发生于儿童的发育性视网膜恶性肿瘤。本研究旨在探讨三结构域蛋白 59（TRIM59）对视网膜母细胞瘤生长的影响及其潜在机制。
我们对基因表达综合数据库中的三个数据集（GSE24673、GSE97508 和 GSE110811）进行了生物信息学分析。采用定量逆转录 PCR 和免疫印迹法检测三种视网膜母细胞瘤细胞系中 TRIM59 的差异表达。采用特异性 siRNA 抑制 HXO-Rb44 细胞系中 TRIM59 的表达。将慢病毒载体转染至 Y79 细胞系以过表达 TRIM59。采用上述细胞系，体外研究 TRIM59 对视网膜母细胞瘤细胞增殖、细胞周期和细胞凋亡的影响。在小鼠异种移植肿瘤模型中评估 TRIM59 表达对视网膜母细胞瘤细胞增殖的影响。
与正常对照相比，三种视网膜母细胞瘤细胞系中 TRIM59 的表达明显升高。在 HXO-Rb44 细胞中，敲低 TRIM59 表达可显著抑制细胞增殖和生长，并促进细胞凋亡，而 TRIM59 过表达则促进 Y79 细胞中的肿瘤进展。沉默 TRIM59 也显著抑制异种移植模型中的体内肿瘤生长。机制研究表明，TRIM59 上调了视网膜母细胞瘤细胞中磷酸化 p38、p-JNK1/2、p-ERK1/2 和 p-c-JUN 的表达。值得注意的是，p38 抑制剂 SB203580 可减弱 TRIM59 对细胞增殖、凋亡和 G1/S 期转换的影响。
TRIM59 在视网膜母细胞瘤中发挥致癌作用，通过激活 p38-丝裂原活化蛋白激酶通路发挥其促肿瘤功能。
