Souidi, M. | Search bioRxiv

bioRxiv2024

Long non-coding RNA UCA1 affects chromatin remodeling via SMARCA2-containing SWI/SNF complex in human colorectal cancer.

Differential lncRNA expression has been correlated to clinical characteristics of colorectal cancers (CRC), which are the second leading cause of cancer-related deaths. LncRNA UCA1 plays a role in epigenetic gene regulation in diverse cancers. We studied CRC cell properties in CRISPR/Cas9 HT29-derived models and, interestingly, UCA1-depleted HT29 cells presented an increased stem-cell phenotype. We show that loss of UCA1 affected SWI/SNF chromatin remodeling complexes, which are previously shown to be involved in maintaining stem-cell properties. Not only was UCA1 permissive for induced SWI/SNF subunit SMARCA2 (BRM) expression upon chemo-drug treatment, but it also affected subunit compositions of SWI/SNF complexes by direct interaction of UCA1 with both ATP helicase BRM and BRG1. UCA1 is known to stimulate proliferation and decrease apoptosis, and we here show that it can restrain cells from a stem cell phenotype. The dual action of UCA1 revealed in this study highlights the complex actions of lncRNAs in cancer.

cancer biology↗

bioRxiv2019

Effects of repetitive Iodine Thyroid Blocking on the Development of the Foetal Brain and Thyroid in rats: a Systems Biology approach

A single dose of potassium iodide (KI) against repeated exposure to radioactive iodine, such as the one of the Fukushima accident, might not be effective enough to protect the thyroid. Our group showed that repetitive dose of KI for eight days offers efficient protection without toxic effects in adult rats. However, the effect of repetitive KI on the developing foetus still unknown especially on brain development, but a correlation between the impaired maternal thyroid status and a decrease in intelligence quotient has been observed. In this study, gene expression analysis of the progeny of repetitive KI-administered pregnant rats performed by our group showed distinct gene expression profile from two different organs: thyroid and cortex. To understand how these differentially expressed genes are implicated in the observed behaviour change, a systems biology approach was used to construct networks using three different techniques; Bayesian statistics using ShrinkNet, sPLS-DA on the DIABLO platform using mixOmics and manual construction of a Process Descriptive network. For each organ, we were able to construct gene expression network, to select genes that are most contributing to either control or KI-treated groups, respectively, and to construct the PD network from differentially expressed (DE) gene enriched with data from publications. Furthermore, we were able to connect DE genes from both organs into one network with genes from both organ participating in the same cellular processes that affect mitophagy and neuronal outgrowth.\n\nThis work may help to evaluate the doctrine for using KI in case of repetitive or prolonged exposure to radioactive particles upon nuclear accidents.

systems biology↗