0000000000790204
AUTHOR
Zhihui Liu
showing 3 related works from this author
Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
2017
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…
Targeting the chromosomal passenger complex subunit INCENP induces polyploidization, apoptosis and senescence in neuroblastoma
2019
Abstract Chromosomal passenger complex (CPC) has been demonstrated to be a potential target of cancer therapy by inhibiting Aurora B or survivin in different types of cancer including neuroblastoma. However, chemical inhibition of either Aurora B or survivin does not target CPC specifically due to off-target effects or CPC-independent activities of these two components. In a previous chromatin-focused siRNA screen, we found that neuroblastoma cells were particularly vulnerable to loss of INCENP, a gene encoding a key scaffolding component of the CPC. In this study, INCENP was highly expressed by neuroblastoma cells, and its expression decreased following retinoic acid–induced neuroblastoma …
Targeting MYCN in Pediatric and Adult Cancers
2021
The deregulation of theMYCfamily of oncogenes, includingc-MYC,MYCNandMYCLoccurs in many types of cancers, and is frequently associated with a poor prognosis. The majority of functional studies have focused onc-MYCdue to its broad expression profile in human cancers. The existence of highly conserved functional domains betweenMYCNandc-MYCsuggests thatMYCNparticipates in similar activities.MYCencodes a basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor (TF) whose central oncogenic role in many human cancers makes it a highly desirable therapeutic target. Historically, as a TF, MYC has been regarded as “undruggable”. Thus, recent efforts focus on investigating methods to indi…