SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells.
SOX4 Mediates ATRA-Induced Differentiation in Neuroblastoma Cells.
复制标题
作者：
神经母细胞瘤（NB）被认为是由神经嵴细胞分化失败引起的。研究人员正致力于探索NB细胞分化的机制，以提高治愈率。在这里，我们的研究结果表明，SOX 4对NB细胞增殖，细胞的神经突起和细胞周期有显着的影响，SOX 4介导的RA在NB细胞中的作用。这表明SOX 4可能是诱导NB细胞分化的靶点。神经母细胞瘤（NB）是儿童颅外最常见的恶性实体瘤，被认为是由神经嵴细胞分化障碍引起的。NB患者的肿瘤分化程度与生存率密切相关。为了探索介导NB细胞分化的潜在靶点，我们分析了来自GEO的四个微阵列数据集，并使用维恩图显示重叠的下调或上调的DEG。SOX 4是重叠上调的DEG之一，并且在ATRA处理的NGP、SY 5 Y和BE 2细胞中通过RT-qPCR和蛋白质印迹证实。为了明确SOX 4是否是调控NB细胞分化的靶基因，通过R2数据库分析SOX 4表达与临床患者生存期的相关性，产生SOX 4过表达质粒和siRNA以改变SOX 4的表达，通过RT-qPCR和Western blot检测SOX 4表达，通过IncuCyte Zoom或CCK 8测定法检测细胞融合或细胞存活，免疫细胞化学染色检测细胞突起，PI染色后流式细胞仪分析细胞周期。结果表明，SOX 4表达与NB细胞的存活率呈正相关，过表达SOX 4可抑制NB细胞增殖，使细胞突起延长，并使细胞周期阻滞于G1期，而敲低SOX 4表达可部分逆转ATRA对NB细胞增殖的抑制、细胞突起的延长，和细胞周期阻滞在G1期。这表明SOX 4可能是诱导NB细胞分化的靶点。
Neuroblastoma (NB) is considered to be caused by the differentiation failure of neural crest cells. Researchers are working on exploring the mechanisms of NB cell differentiation to improve the cure rate. Here, our results show that SOX4 has a significant effect on NB cell proliferation, cells’ neurites, and the cell cycle and that SOX4 mediates the effect of RA in NB cells. All indicate that SOX4 may be a target to induce NB cell differentiation. Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells’ neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells’ neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells’ neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation.
登录
查看更多内容
影响因子：
3.8
作者：
Inoue H;Takahashi H;Hashimura M;Eshima K;Akiya M;Matsumoto T;Saegusa M
通讯作者：
Saegusa M
影响因子：
11.2
作者：
Lee H;Goodarzi H;Tavazoie SF;Alarcón CR
通讯作者：
Alarcón CR
影响因子：
16.6
作者：
Hatori Y;Yan Y;Schmidt K;Furukawa E;Hasan NM;Yang N;Liu CN;Sockanathan S;Lutsenko S
通讯作者：
Lutsenko S
影响因子：
8
作者：
Peterson, S;Bogenmann, E
通讯作者：
Bogenmann, E
影响因子：
8.8
作者：
通讯作者：
--