ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury

Jie Chen, Li Yan, Haosen Wang, Zengmeng Zhang, Daolun Yu, Chaofeng Xing, Jie Li, Honglin Li, Jun Li, Yafei Cai

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Apoptosis is an important contributing factor in spinal cord injury (SCI). ZBTB38 is involved in the transcriptional regulation of multiple signaling pathways, is differentially expressed at different SCI stages, and may provide a therapeutic strategy for the treatment of patients with SCI. In this study, we found that autophagy is blocked in ZBTB38 knockdown SH-SY5Y cells and that the expression levels of LC3B II/I decreased and P62 increased. We used transcriptome high-throughput sequencing to identify the target in ZBTB38 knockdown cells. From the transcriptome profile, RB1CC1 (i.e., FIP200), a key component of the initiation machinery of autophagy (FIP200-ATG13-ULK1-ATG101), was found to decrease 4.2-fold following ZBTB38 knockdown. When RB1CC1-overexpressed plasmids were transfected into ZBTB38 knockdown cells, they rescued the phenotype of ZBTB38 knockdown cells. Cell proliferation and viability were significantly enhanced by RB1CC1 overexpression, and LC3B and P62 expression returned to their original levels. We also injected ZBTB38-overexpressed lentivirus into the injured center of the spinal cord and detected significant upregulation of RB1CC1 in the spinal cord. ZBTB38 overexpression can promote autophagy and partly rescue the secondary damage of SCI. Therefore, our findings provide a new strategy for the treatment of SCI.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalGene
Volume678
DOIs
StatePublished - Dec 15 2018

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Keywords

  • Autophagy
  • RB1CC1
  • RNA sequencing
  • Spinal Cord Injury
  • ZBTB38

ASJC Scopus subject areas

  • Genetics

Cite this

Chen, J., Yan, L., Wang, H., Zhang, Z., Yu, D., Xing, C., Li, J., Li, H., Li, J., & Cai, Y. (2018). ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury. Gene, 678, 8-16. https://doi.org/10.1016/j.gene.2018.07.073