Title:Detection of Melanogenesis and Anti-Apoptosis-Associated Melanoma
Factors: Array CGH and PPI Mapping Integrating Study
Volume: 28
Issue: 12
Author(s): Shang-Jun Yin, Guo-Ying Qian, Jun-Mo Yang, Jinhyuk Lee*Yong-Doo Park*
Affiliation:
- Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Gwahak-ro,
Yuseong-gu, Daejeon, 34141, Korea
- Department of Bioinformatics, KRIBB school of Bioscience, University of Science
and Technology (UST), 217 Gajung-ro, Yuseong-gu, Daejeon 34113, Korea
- College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, P.R. China
- Skin Diseases Research Center,
Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, P.R. China
- Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, P.R. China
Keywords:
Melanoma, array CGH, PPI mapping, molecular dynamics simulation, YWHAB, melanogenesis.
Abstract: Background: We investigated melanogenesis- and anti-apoptosis-related melanoma factors
in melanoma cells (TXM1, TXM18, A375P, and A375SM).
Objective: To find melanoma associated hub factor, high-throughput screening-based techniques integrating
with bioinformatics were investigated.
Methods: Array CGH analysis was conducted with a commercial system. Total genomic DNAs prepared
individually from each cell line with control DNA were properly labeled with Cy3-dCTP and
Cy5-dCTP and hybridizations and subsequently performed data treatment by the log2 green (G;
test) to red (R; reference) fluorescence ratios (G/R). Gain or loss of copy number was judged by
spots with log2-transformed ratios. PPI mapping analysis of detected candidate genes based on the
array CGH results was conducted using the human interactome in the STRING database. Energy
minimization and a short Molecular Dynamics (MD) simulation using the implicit solvation model
in CHARMM were performed to analyze the interacting residues between YWHAZ and YWHAB.
Results: Three genes (BMP-4, BFGF, LEF-1) known to be involved in melanogenesis were found
to lose chromosomal copy numbers, and Chr. 6q23.3 was lost in all tested cell lines. Ten hub genes
(CTNNB1, PEX13, PEX14, PEX5, IFNG, EXOSC3, EXOSC1, EXOSC8, UBC, and PEX10) were
predicted to be functional interaction factors in the network of the 6q23.3 locus. The apoptosis-associated
genes E2F1, p50, BCL2L1, and BIRC7 gained, and FGF2 lost chromosomal copy numbers
in the tested melanoma cell lines. YWHAB, which gained chromosomal copy numbers, was predicted
to be the most important hub protein in melanoma cells. Molecular dynamics simulations for
binding YWHAB and YWHAZ were conducted, and the complex was predicted to be energetically
and structurally stable through its 3 hydrogen-bond patterns. The number of interacting residues is
27.
Conclusion: Our study compares genome-wide screening interactomics predictions for melanoma
factors and offers new information for understanding melanogenesis- and anti-apoptosis-associated
mechanisms in melanoma. Especially, YWHAB was newly detected as a core factor in melanoma
cells.
