The ubiquitin proteasome system regulates key cellular processes in normal and in cancer cells. Herein, we review published data on the role of ubiquitin ligases in the four major subgroups of medulloblastoma (MB). While conventional literature serves as an initial source of information on cellular pathways in MB, large publicly available datasets of gene expression can be used to add information not previously identified in the literature. By analysing the publicly available Cavalli dataset, we show that increased expression of ZNRF3 characterizes the WNT subgroup of MB. The ZNRF3 gene codes for an E3 ligase associated with WNT receptors. Loss of a copy of chromosome 6 in a subtype of the WNT group was associated with decreased expression of the gene encoding the E3 ligase RNF146. While the E3 ligase SMURF regulates SHH receptors, increased expression of the gene encoding the Cullin Ring E3 adaptor PPP2R2C was statistically a better genetic marker of the SHH group. Genes whose expression was statistically strongly related to Group 3 included the E3 ligase gene TRIM58, and the gene for the E3 ligase adaptor, PPP2R2B. Group 4 MB was associated with expression of genes encoding several E3 ligases and E3 ligase adaptors involved in ribosome biogenesis. Increased expression of the genes encoding the E3 ligase adaptors and transcription repressors ZBTB18 and ZBTB38 were also noted in subgroup 4. These data suggest that several E3 ligases and their adaptors should be investigated as therapeutic targets for subgroup specific MB brain tumors.

中文翻译：

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泛素连接酶和髓母细胞瘤：通过转录组数据集鉴定的四个共有亚组的遗传标记。

泛素蛋白酶体系统调节正常细胞和癌细胞中的关键细胞过程。在这里，我们审查有关泛素连接酶在髓母细胞瘤（MB）的四个主要亚组中的作用的公开数据。尽管常规文献充当了MB细胞通路途径的信息的原始来源，但是大量的公共可用基因表达数据集可用于添加文献中以前未发现的信息。通过分析可公开获得的Cavalli数据集，我们显示ZNRF3的表达增加是MB WNT亚组的特征。ZNRF3基因编码与WNT受体相关的E3连接酶。WNT组亚型中6号染色体拷贝的丢失与编码E3连接酶RNF146的基因的表达降低有关。尽管E3连接酶SMURF调节SHH受体，从统计学上讲，编码Cullin Ring E3接头PPP2R2C的基因表达增加，是SHH组更好的遗传标记。其表达在统计学上与第3组密切相关的基因包括E3连接酶基因TRIM58和E3连接酶适配器PPP2R2B的基因。组4 MB与编码参与核糖体生物发生的几种E3连接酶和E3连接酶衔接子的基因的表达有关。在亚组4中也注意到了编码E3连接酶衔接子和转录阻遏物ZBTB18和ZBTB38的基因表达增加。这些数据表明，应研究几种E3连接酶及其衔接子作为亚组特异性MB脑肿瘤的治疗靶标。其表达在统计学上与第3组密切相关的基因包括E3连接酶基因TRIM58和E3连接酶适配器PPP2R2B的基因。组4 MB与编码参与核糖体生物发生的几种E3连接酶和E3连接酶衔接子的基因的表达有关。在亚组4中也发现了编码E3连接酶衔接子和转录阻遏物ZBTB18和ZBTB38的基因表达增加。这些数据表明，应研究几种E3连接酶及其衔接子作为亚组特异性MB脑肿瘤的治疗靶标。其表达在统计学上与第3组密切相关的基因包括E3连接酶基因TRIM58和E3连接酶适配器PPP2R2B的基因。组4 MB与编码参与核糖体生物发生的几种E3连接酶和E3连接酶衔接子的基因的表达有关。在亚组4中也注意到了编码E3连接酶衔接子和转录阻遏物ZBTB18和ZBTB38的基因表达增加。这些数据表明，应研究几种E3连接酶及其衔接子作为亚组特异性MB脑肿瘤的治疗靶标。