Network models for understanding boron-induced transcriptomics changes within HepG2 cell line

Tombuloğlu, Ayşegül
Çöpoğlu, Hülya
Güray, Nülüfer Tülün
Son Aydın, Yeşim
Boron has crucial roles in plant growth and survival; also, it is suggested as an essential trace element forhuman physiology. Accumulating evidence show beneficial effects of boron for human health. Along withits benefits to bone and brain health, many findings support the anti-carcinogenic role of dietary boron.Although biochemical significance of boron is evident, relatively few studies focus on boron-inducedbiological processes and mechanisms at the molecular level.In this work, we aim to reveal the boron-induced molecular mechanisms in detail, and our preliminaryfindings of network modelling studies is presented. HepG2 cell line is treated with boric acid (BA) at halfmaximalinhibitory concentration (IC50) for 24 hours. Differential gene expression profile relative to nontreatedHepG2 cells is investigated with microarray technology. Gene expression changes in HepG2 cellscultured with different chemicals are also obtained by re-analysis of published data, and integrated withgene expression changes due to boric acid treatment. Integrated gene expression data is used forreconstructing a weighted gene co-expression network to investigate the bioactivity of boric acid in acomparative manner. As a second approach, a regulatory network is build using boric acid induced geneexpression data with motif knowledge and known physical interactions among transcription factors.84At half-maximal inhibitory concentration, boric acid treatment lead to a massive down-regulation ofgenes which take part in in cell-cycle progression and various metabolic processes. Few genes involved inapoptosis and cytokine-cytokine receptor interaction pathway had elevated levels of expression in thepresence of boric acid exposure. Comparative network analysis indicated the induction of manyfunctional gene groups, which appear to be specifically associated with boric acid treatment. Regulatorynetwork revealed transcription factor-gene interactions, which will help us to exploit the effectedregulatory mechanisms at transcriptomics level in the presence of highly concentrated boron.According to our results, a group of genes involved in lipid metabolism might be particularly meaningfulsince latest research suggest potential therapeutic activity of boron in lipid dysregulation disorders likefatty liver disease and obesityThese genes were down-regulated in boric acid treated cells and formed aboric acid associated subnetwork contrasting with the carcinogenic chemical induced profile. In thefuture we plan to validate the key proteins in the regulatory network in cell culture. Moreover, we aim torecapitulate the microarray experiments and carry out subsequent network modelling at lowerconcentrations of boric acid to study the boric acid related network patterns in a concentrationdependent manner.
HIBIT2018 11th International Symposium on Health Informatics and Bioinformatics (25 - 27 Ekim 2018)


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Citation Formats
A. Tombuloğlu, H. Çöpoğlu, N. T. Güray, and Y. Son Aydın, “Network models for understanding boron-induced transcriptomics changes within HepG2 cell line,” Antalya, Türkiye, 2018, p. 83, Accessed: 00, 2021. [Online]. Available: