ZBTB38 gene knockdown Human neuroblastoma cells Raw sequence reads. Homo sapiens

Transcription factor ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. Only several predicted BTB domain-containing proteins encoded in the human genome have been functionally characterized. No relevant studies have been reported concerning the effect of down-regulated ZBTB38 gene expression on tumor cells through transcriptome analysis. In the present study, 2,438 differentially expressed genes in ZBTB38-/- SH-SY5Y cells were obtained via high-throughput transcriptome sequencing analysis, 83.5% of which was down-regulated. Furthermore, GO functional clustering and KEGG pathway enrichment analysis of these differentially expressed genes (DEGs) revealed that the knocked-down transcription factor ZBTB38 interacted with p53 and arrested cell cycles to inhibit the proliferation of the tumor cells. Besides, it also significantly down-regulated the expressions of PTEN, a "molecular switch" of the PI3K/Akt signaling pathway, and RB1CC1, the key gene for autophagy initiation, and blocked autophagy to accelerate the apoptosis of tumor cells. ZBTB38-/- SH-SY5Y cells were investigated at the whole transcriptome level and key DEGs were screened in the present study, providing a theoretical foundation for exploring the molecular mechanism of inhibition of tumor cell proliferation and targeted anti-tumor therapies.

转录因子ZBTB38（Transcription factor ZBTB38）隶属于锌指蛋白家族，携带有典型的BTB结构域（BTB domain）。目前人类基因组中仅有数个预测的含BTB结构域的蛋白完成了功能鉴定。尚未有研究通过转录组分析报道下调ZBTB38基因表达对肿瘤细胞的相关影响。本研究通过高通量转录组测序分析，在ZBTB38基因敲除的SH-SY5Y细胞中筛选得到2438个差异表达基因（differentially expressed genes, DEGs），其中83.5%的基因表达量呈下调趋势。对上述差异表达基因进行GO功能聚类分析与KEGG通路富集分析后发现，敲低转录因子ZBTB38可与p53产生相互作用，阻滞细胞周期进程以抑制肿瘤细胞增殖。此外，该因子还可显著下调PI3K/Akt信号通路的“分子开关”PTEN的表达，以及自噬起始关键基因RB1CC1的表达，进而阻断细胞自噬过程，加速肿瘤细胞凋亡。本研究在全转录组水平对ZBTB38基因敲除的SH-SY5Y细胞进行了系统分析，筛选得到关键差异表达基因，为探索肿瘤细胞增殖抑制的分子机制及靶向抗肿瘤治疗提供了理论基础。