Cell Death and Disease (Nov 2024)

KHDRBS1 regulates the pentose phosphate pathway and malignancy of GBM through SNORD51-mediated polyadenylation of ZBED6 pre-mRNA

  • Xiaoyu Liu,
  • Xiaobai Liu,
  • Weiwei Dong,
  • Ping Wang,
  • Libo Liu,
  • Lu Liu,
  • Tiange E,
  • Di Wang,
  • Yang Lin,
  • Hongda Lin,
  • Xuelei Ruan,
  • Yixue Xue

DOI
https://doi.org/10.1038/s41419-024-07163-x
Journal volume & issue
Vol. 15, no. 11
pp. 1 – 15

Abstract

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Abstract Glioblastoma is one of the most common and aggressive primary brain tumors. The aberration of metabolism is the important character of GBM cells and is tightly related to the malignancy of GBM. We mainly verified the regulatory effects of KHDRBS1, SNORD51 and ZBED6 on pentose phosphate pathway and malignant biological behavior in glioblastoma cells, such as proliferation, migration and invasion. KHDRBS1 and SNORD51 were upregulated in GBM tissues and cells. But ZBED6 had opposite tendency in GBM tissues and cells. KHDRBS1 may improve the stability of SNORD51 by binding to SNORD51, thus elevating the expression of SNORD51. More importantly, SNORD51 can competitively bind to WDR33 with 3’UTR of ZBED6 pre-mRNA which can inhibit the 3’ end processing of ZBED6 pre-mRNA, thereby inhibiting the expression of ZBED6 mRNA. ZBED6 inhibited the transcription of G6PD by binding to the promoter region of G6PD. Therefore, the KHDRBS1/SNORD51/ZBED6 pathway performs an important part in regulating the pentose phosphate pathway to influence malignant biological behavior of GBM cells, providing new insights and potential targets for the treatment of GBM.