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
3309 - Heat Shock Protein 90 chaperones and Protein Kinase D3 regulates androgen-independent prostate cancer development
Presenter: Attila Varga
Session: Poster Display session 1
Resources:
Abstract
3441 - The SWI/SNF driven reprograming for the AR cistrome is NSD2 dependent
Presenter: Katia Ruggero
Session: Poster Display session 1
Resources:
Abstract
1659 - IGF1R inhibition affects the survival of HT29 cancer cells by alterations of the TLR9- and autophagy signaling
Presenter: Györgyi Műzes
Session: Poster Display session 1
Resources:
Abstract
1379 - Characterization of atypical dMMR (deficient MisMatch Repair) tumors: a study from a large cohort of 4948 cases
Presenter: Marion Jaffrelot
Session: Poster Display session 1
Resources:
Abstract
1657 - Modulation of TLR9-dependent autophagy response via inhibition of c-Met signaling influences the survival of HT29 cancer cells
Presenter: Ferenc Sipos
Session: Poster Display session 1
Resources:
Abstract
3045 - Positive Feedback Activation of Notch Signal by Obesity Enhances Colorectal Tumorigenicity
Presenter: Dake Chu
Session: Poster Display session 1
Resources:
Abstract
3210 - Protein tyrosine phosphatase non-receptor type 3 (PTPN3) could be a new therapeutic target for pancreatic cancer.
Presenter: Akio Yamasaki
Session: Poster Display session 1
Resources:
Abstract
3920 - A Novel bispecific BCMAxCD3 T cell engaging antibody that treat multiple myeloma (MM) with minimal cytokine serection
Presenter: Zhenyu Li
Session: Poster Display session 1
Resources:
Abstract
2691 - Quantitative spatial profiling of lymphocyte-activation gene 3 (LAG-3)/major histocompatibility complex class II (MHC II) interaction in gastric and urothelial tumors
Presenter: Cyrus Hedvat
Session: Poster Display session 1
Resources:
Abstract
2182 - Evaluating the prevalence of the expression of PD-L1 in NSCLC specimens with short-duration formalin fixation using IHC 22C3 pharmDx
Presenter: Keiichi Ota
Session: Poster Display session 1
Resources:
Abstract