Therapeutic Targeting of MZF1-AS1/PARP1/E2F1 Axis Inhibits Proline Synthesis and Neuroblastoma Progression.

ABSTRACT: Proline synthesis plays an important role in the metabolic reprogramming that contributes to tumor progression. However, the mechanisms regulating expression of proline synthetic genes in neuroblastoma (NB) remain elusive. Herein, through integrative screening of a public dataset and amino acid profiling analysis, myeloid zinc finger 1 (MZF1) and MZF1 antisense RNA 1 (MZF1-AS1) are identified as transcriptional regulators of proline synthesis and NB progression. Mechanistically, transcription factor MZF1 promotes the expression of aldehyde dehydrogenase 18 family member A1 and pyrroline-5-carboxylate reductase 1, while proline facilitates the aggressiveness of NB cells. In addition, MZF1-AS1 binds poly(ADP-ribose) polymerase 1 (PARP1) to facilitate its interacti

SUBMITTER: Fang E 

PROVIDER: S-EPMC6774027 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature