Functional analysis of HBO1 in tumor development and inhibitor screening

  • Authors:
    • Ling-Li Guo
    • Su-Yang Yu
    • Meng Li
  • View Affiliations

  • Published online on: May 31, 2016     https://doi.org/10.3892/ijmm.2016.2617
  • Pages: 300-304
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The aim of the present study was to explore the functions of histone acetyltransferase binding to origin recog­nition complex (ORC) 1 (HBO1) during tumor development and to screen for HBO1 inhibitors. The chromatin immuno­precipitation sequencing (ChIP-seq) data of HBO1 in the RKO human colon cancer cell line (GSE33007) were downloaded from the Gene Expression Omnibus (GEO) database. The reads were then mapped back to a reference genome hg19. The PCR duplicate reads were removed by using SAMtools software and the shift was calculated using SPP and MaSC software. The peak calling was carried out using MACS 1.4.0 software. Furthermore, the inhibitors of HBO1 were screened out from the Specs database using Dock 6.6 software. The binding sites of HBO1 were mainly distributed in the intergenic, intronic and 3'-end regions. Further analysis revealed that a total of 9,467 target genes was identified around HBO1 binding sites in the RKO cell lines and those genes mainly participated in the cell cycle, biosynthetic process, as well as other processes. Finally, 5 inhibitors with best binding affinity in the positively charged cavity of HBO1 were screened out: i) 5-[(2-hydroxybenzylidene)amino] -2-(2‑{4‑[(2‑hydroxy­benzylidene)amino]-2-sulfonatophenyl}vinyl)benzenesulfonate, ii) 3-[4-(3-bromo-4-{2-[4-(ethoxycarbonyl)anilino]-2-oxo­ethoxy}-5-methoxybenzylidene)‑3‑methyl‑5‑oxo -4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, iii) 4-(4-{3-iodo‑5‑ methoxy‑4-[2-(2-methoxyanilino)-2-oxoethoxy]benzylidene}-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid, iv) 5-chloro-1,3-bis{[3,5,6-trihydroxy-4-(octyloxy)tetrahydro-2H-pyran-2-yl]methyl}-1,3-dihydro-2H-benzimidazol-2-one and v) 4-{[4-(tetradecylamino)-1-naphthyl]diazenyl}benzoic acid. As a whole, in this study, we identified the possible binding sites and biological functions of HBO1. The potential inhibitors of HBO1 were also screened, which prove to be helpful for the inhibition of HBO1 during tumor development.
View Figures
View References

Related Articles

Journal Cover

July-2016
Volume 38 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Guo L, Yu S and Li M: Functional analysis of HBO1 in tumor development and inhibitor screening. Int J Mol Med 38: 300-304, 2016.
APA
Guo, L., Yu, S., & Li, M. (2016). Functional analysis of HBO1 in tumor development and inhibitor screening. International Journal of Molecular Medicine, 38, 300-304. https://doi.org/10.3892/ijmm.2016.2617
MLA
Guo, L., Yu, S., Li, M."Functional analysis of HBO1 in tumor development and inhibitor screening". International Journal of Molecular Medicine 38.1 (2016): 300-304.
Chicago
Guo, L., Yu, S., Li, M."Functional analysis of HBO1 in tumor development and inhibitor screening". International Journal of Molecular Medicine 38, no. 1 (2016): 300-304. https://doi.org/10.3892/ijmm.2016.2617