Chen Jie, Xing Chaofeng, Yan Li, Wang Yabing, Wang Haosen, Zhang Zongmeng, Yu Daolun, Li Jie, Li Honglin, Li Jun, Cai Yafei
College of Life Sciences, Anhui Provincial Key Lab of the Conservation and Exploitation of Biological Resources, Anhui Normal University, WuHu, China.
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
PeerJ. 2019 Jan 24;7:e6352. doi: 10.7717/peerj.6352. eCollection 2019.
ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. As a transcription factor, ZBTB38 is involved in cell regulation, proliferation and apoptosis, whereas, functional deficiency of ZBTB38 induces the human neuroblastoma (NB) cell death potentially. To have some insight into the role of ZBTB38 in NB development, high throughput RNA sequencing was performed using the human NB cell line SH-SY5Y with the deletion of ZBTB38. In the present study, 2,438 differentially expressed genes (DEGs) in ZBTB38 SH-SY5Y cells were obtained, 83.5% of which was down-regulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the neurotrophin TRK receptor signaling pathway, including PI3K/Akt and MAPK signaling pathway. we also observed that ZBTB38 affects expression of CDK4/6, Cyclin E, MDM2, ATM, ATR, PTEN, Gadd45, and PIGs in the p53 signaling pathway. In addition, ZBTB38 knockdown significantly suppresses the expression of autophagy-related key genes including PIK3C2A and RB1CC1. The present meeting provides evidence to molecular mechanism of ZBTB38 modulating NB development and targeted anti-tumor therapies.
ZBTB38属于锌指蛋白家族,包含典型的BTB结构域。作为一种转录因子,ZBTB38参与细胞调控、增殖和凋亡,而ZBTB38的功能缺陷可能会诱导人类神经母细胞瘤(NB)细胞死亡。为了深入了解ZBTB38在NB发育中的作用,我们使用缺失ZBTB38的人类NB细胞系SH-SY5Y进行了高通量RNA测序。在本研究中,我们获得了ZBTB38缺失的SH-SY5Y细胞中的2438个差异表达基因(DEG),其中83.5%为下调基因。在京都基因与基因组百科全书数据库中对这些DEG进行功能注释发现,大多数鉴定出的基因富集于神经营养因子TRK受体信号通路,包括PI3K/Akt和MAPK信号通路。我们还观察到ZBTB38影响p53信号通路中CDK4/6、细胞周期蛋白E、MDM2、ATM、ATR、PTEN、Gadd45和PIGs的表达。此外,ZBTB38基因敲低显著抑制了包括PIK3C2A和RB1CC1在内的自噬相关关键基因的表达。本研究为ZBTB38调节NB发育的分子机制和靶向抗肿瘤治疗提供了证据。