Abstract 2285
Background
Bromodomain-containing proteins are important epigenetic regulators that specifically recognize acetylated histones and implicated in regulating gene expression. Bromodomain inhibitors showed a prominent therapeutic effect on metabolic diseases and various types of cancers in clinical trials. In this study, we employed RNA-Seq to interrogate the expression profile of bromodomain-containing proteins in human hepatocellular carcinoma (HCC). We found that Bromodomain and PHD Finger Containing 1 (BRPF1) was among the most significantly overexpressed bromodomain-containing proteins in HCC.
Methods
The expression profile of bromodomain-containing proteins in our HCC patients was analyzed by RNA-Seq. BRPF1 knockout in MHCC97L was accomplished by using lentiviral-based CRISPR gene editing system. Cell proliferation, colony formation, and cell migration assays were performed to assess in vitro function of BRPF1. A nude mice orthotopic liver xenograft model was used to study the role of BRPF1 in HCC tumorigenicity and lung metastasis in vivo. Sphere formation assay and qPCR were performed to study the stemness properties of BRPF1 knockdown cells. Apoptosis and cell cycle arrest assay was performed by flow cytometry. Senescence was detected by B-galactosidase staining, mRNA and protein expression of senescence-associated makers.
Results
Clinically, high BRPF1 expression was associated with poorer survival rates in HCC patients. The upregulation of BRPF1 mRNA in HCC was significantly associated with gene copy gain and gene amplification. ROC analysis indicated that BRPF1 was a potential biomarker for HCC detection. shRNA-mediated knockdown and CRISPR-mediated knockout of BRPF1 suppressed cell proliferation and colony formation in MHCC97L. Knockout of BRPF1 also reduced tumorigenicity in liver orthotopic injection model in nude mice. We found that BRPF1 expression was elevated in CD133+ liver cancer stem cells. Inactivation of BRPF1 also reduced the expression of genes related to cancer stemness and cancer renewal ability in sphere formation. BRPF1 inhibition induced apoptosis, cell cycle arrest as well as cellular senescence.
Conclusions
Our findings suggest that BRPF1 may contribute to HCC development and cancer stemness.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4079 - Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy
Presenter: Gabriela Kramer-marek
Session: Poster Display session 1
Resources:
Abstract
4364 - Upregulation of sFRP3 circulating expression levels correlates survival outcomes in glioblastoma
Presenter: Gema Bruixola
Session: Poster Display session 1
Resources:
Abstract
2327 - Characterization and pre-clinical modeling of genetic aberrations in pediatric gliomas
Presenter: Itai Moshe
Session: Poster Display session 1
Resources:
Abstract
3154 - Preclinical Study of Novel Tetracyclic Small Molecule, CC12, for Brain Cancer
Presenter: Liyun Fann
Session: Poster Display session 1
Resources:
Abstract
5759 - CHLOROBRAIN phase IB trial: The addition of chloroquine, an autophagy inhibitor, to concurrent radiation and temozolomide for newly diagnosed glioblastoma
Presenter: Inge Compter
Session: Poster Display session 1
Resources:
Abstract
1382 - A Phase II Clinical Trial Evaluating the Efficacy and Safety of Apatinib Combined with dose-dense Temozolomide in Recurrent Glioblastoma
Presenter: Yong Wang
Session: Poster Display session 1
Resources:
Abstract
4407 - Phase 0 Trial of Ceritinib in Brain Metastases and Recurrent Glioblastoma
Presenter: Shwetal Mehta
Session: Poster Display session 1
Resources:
Abstract
1469 - Pembrolizumab (Pem) in recurrent high-grade glioma (HGG) patients with mismatch repair deficiency (MMRd): an observational study
Presenter: Mario Caccese
Session: Poster Display session 1
Resources:
Abstract
4217 - Outcome of high-grade gliomas (HGGs) treated into immunotherapeutic early-phase clinical trials (ieCTs): a single-center experience
Presenter: Matteo Simonelli
Session: Poster Display session 1
Resources:
Abstract
5107 - Tolerability of PCV in Low Grade Glioma: a Real World Experience
Presenter: Razia Aslam
Session: Poster Display session 1
Resources:
Abstract