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
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract