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

HIBIT2018 11th International Symposium on Health Informatics and Bioinformatics, Antalya, Türkiye, 25 - 27 Ekim 2018, ss.83-84

Network models for understanding boron-induced transcriptomics changes within HepG2

cell line

Ayşegül Tombuloğlu, Hülya Çöpoğlu, Tülin Güray and Yeşim Aydın Son

Middle East Technical University, Graduate School of Informatics, Health Informatics

Department {yesim@metu.edu.tr}

Boron has crucial roles in plant growth and survival; also, it is suggested as an essential trace element for

human physiology. Accumulating evidence show beneficial effects of boron for human health. Along with

its 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-induced

biological processes and mechanisms at the molecular level.

In this work, we aim to reveal the boron-induced molecular mechanisms in detail, and our preliminary

findings of network modelling studies is presented. HepG2 cell line is treated with boric acid (BA) at halfmaximal

inhibitory concentration (IC50) for 24 hours. Differential gene expression profile relative to nontreated

HepG2 cells is investigated with microarray technology. Gene expression changes in HepG2 cells

cultured with different chemicals are also obtained by re-analysis of published data, and integrated with

gene expression changes due to boric acid treatment. Integrated gene expression data is used for

reconstructing a weighted gene co-expression network to investigate the bioactivity of boric acid in a

comparative manner. As a second approach, a regulatory network is build using boric acid induced gene

expression data with motif knowledge and known physical interactions among transcription factors.

At half-maximal inhibitory concentration, boric acid treatment lead to a massive down-regulation of

genes which take part in in cell-cycle progression and various metabolic processes. Few genes involved in

apoptosis and cytokine-cytokine receptor interaction pathway had elevated levels of expression in the

presence of boric acid exposure. Comparative network analysis indicated the induction of many

functional gene groups, which appear to be specifically associated with boric acid treatment. Regulatory

network revealed transcription factor-gene interactions, which will help us to exploit the effected

regulatory 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 meaningful

since latest research suggest potential therapeutic activity of boron in lipid dysregulation disorders like

fatty liver disease and obesityThese genes were down-regulated in boric acid treated cells and formed a

boric acid associated subnetwork contrasting with the carcinogenic chemical induced profile. In the

future we plan to validate the key proteins in the regulatory network in cell culture. Moreover, we aim to

recapitulate the microarray experiments and carry out subsequent network modelling at lower

concentrations of boric acid to study the boric acid related network patterns in a concentration

dependent manner.