Biology subjects

Kahnamoui, S.

Publications and source records attributed to Kahnamoui, S..

3 recordsLinked to original sources

bioRxiv2025

Dysregulated circRNA expression profile and associated miRNA sponging in abnormal lung development in congenital diaphragmatic hernia

RationaleCircular RNAs (circRNAs) can function as disease biomarkers. Their profile in abnormal lung development in congenital diaphragmatic hernia (CDH) is unknown. ObjectiveTo evaluate circRNA expression profile in CDH-associated abnormal lung development. MethodsWe profiled circRNAs in rat CDH and control lungs at embryonic day (E)15 and E21 by microarray. We validated identified circRNAs using back-splice junction amplicon sequencing, RT-qPCR, and in situ hybridization. We modified a CircRNA Function prediction Tool to predict CircRNA::micro(mi)RNA::messenger(m)RNA interactions and compared these with Oxford Nanopore RNA sequencing and existing human CDH datasets. Measurements and Main ResultsMicroarrays revealed a unique circRNA biosignature during CDH lung development. CircAnp32e was expressed in a sex-specific and spatiotemporal expression pattern in the epithelium at E15. The predicted mature sequence of circAnp32e overlapped >90% with its human orthologue. CircRNA::miRNA::mRNA interaction networks in E15 and E21 revealed enrichment in inflammation/infection, smooth muscle cell function, cell proliferation/cell cycle regulation, and response to hypoxia pathways. Parental genes of differential expressed circRNAs at E15 enriched pathways linked to cell proliferation/cell cycle/cancer, while at end-gestation, inflammation and cardiovascular processes were also overrepresented. Rat and human CDH lungs showed overlapping pathways with additional enrichment for RNA processing and protein binding/modification in humans. ConclusionA unique circRNA signature during abnormal lung development in CDH may mediate inflammatory responses, smooth-muscle-cell function, and cell proliferation regulation via miRNA sponging. Overlap of downstream pathways in rat and human CDH suggest conserved functions across species. CircRNAs may serve as biomarkers to guide prenatal management and mitigate aberrant lung development in CDH.

developmental biology↗

bioRxiv2023

Novel DNA methylation changes in mouse lungs associated with heavy smoking

Smoking is a potent cause of asthma, chronic obstructive pulmonary disease (COPD) and many other health defects, and changes in DNA methylation (DNAm) have been identified as a potential link between smoking and these health outcomes. However, most links between smoking and DNAm have been made using blood and other easily accessible tissues in humans, while evidence from more directly affected tissues such as the lungs is greatly lacking. Here, we identified DNAm patterns which are altered by smoking directly in the lungs. We used a well-established mouse model to measure the effects of heavy smoking first on lung phenotype immediately after smoking and then after a period of smoking cessation. Next, we determined whether our mouse model could recapitulate previous DNAm patterns observed in smoking humans by measuring DNAm at a candidate gene responsive to cigarette smoke (CS), Cyp1a1. Finally we carried out epigenome-wide DNAm analyses using the newly released Illumina mouse methylation microarrays. Our results recapitulate some of the phenotypes and DNAm patterns observed in human studies but reveal 32 differentially methylated genes specific to the lungs which have not been previously associated with smoking. The affected genes are known to be involved in nicotine dependency, tumorigenesis and metastasis, immune cell dysfunction, lung function decline, and COPD. This research emphasizes the need to study CS-mediated DNAm signatures in directly affected tissues like the lungs, as that may be essential in understanding mechanisms underlying CS-mediated health outcomes.

molecular biology↗

bioRxiv2023

Early life exposure to cigarette smoke is associated with lung function changes and primes gene expression and DNA methylation changes at Cyp1a1 upon exposure later in life

Prenatal and early life exposure to cigarette smoke (CS) have repeatedly been shown to induce stable, long-term changes in DNA methylation (DNAm) in offspring. It has been hypothesized that these changes might be functionally related to the known outcomes of prenatal and early life CS exposure, which include impaired lung development, altered lung function and increased risk of asthma and wheeze. However, to date, few studies have examined DNAm changes induced by prenatal CS in tissues of the lung, and even fewer have attempted to examine the specific influences of prenatal versus early postnatal exposures. Here, we have established a mouse model of CS exposure which isolates the effects of prenatal and early postnatal CS exposures in early life. We have used this model to measure the effects of prenatal and/or postnatal CS exposures on lung function and immune cell infiltration as well as DNAm and expression of Cyp1a1, a candidate gene previously observed to demonstrate DNAm differences upon CS exposure in humans. Our study revealed that exposure to CS prenatally and in the early postnatal period cause long-lasting differences in offspring lung function, gene expression and lung Cyp1a1 DNAm, which wane over time but are reestablished upon re-exposure to CS in adulthood. This study creates a testable mouse model which can be used to investigate the effects of prenatal and early postnatal CS exposures and will contribute to the design of intervention strategies to mediate these detrimental effects.

genetics↗