Biology subjects

Badaoui, B.

Publications and source records attributed to Badaoui, B..

4 recordsLinked to original sources

bioRxiv2025

Integrative transcriptomic analysis identifies miR-642a-5p as a regulator of POFUT1 expression in colon cancer

BackgroundColorectal cancer (CRC) is one of the most common and deadly cancers worldwide, underscoring the urgent need for novel biomarkers and therapeutic targets. Protein O-fucosyltransferase 1 (POFUT1) is increasingly recognized as an oncogenic driver in CRC, but the upstream regulatory mechanisms responsible for its overexpression remain poorly understood. ObjectiveWe aimed to identify a reproducible miRNA signature potentially regulating POFUT1 in colon cancer by combining multiple computational approaches and intersecting their outcomes to retain the most significant candidates and to validate biologically the most promising miRNA to confirm its regulatory potential. MethodsWe implemented an integrative, multi-step bioinformatics framework that combined multiple linear regression with stepwise selection, penalized regression models (LASSO and Elastic Net), and Random Forest analysis for non-linear feature evaluation. miRNAs showing a consistent inverse association with POFUT1 across these complementary methods were retained as final candidates. The most significant miRNA was then validated in vitro by mimic transfection, real-time quantitative PCR, and dual-luciferase reporter assays performed in colon cancer cell lines. ResultsFive miRNAs (miR-92b, miR-484, miR-574, miR-642a, and miR-3940) were consistently identified as negative contributors to POFUT1 expression across all analytical approaches. Among these, miR-642a exhibited the strongest negative correlation (r = - 0.44) with POFUT1. It was therefore selected for biological validation to confirm its regulatory interaction. Overexpression of miR-642a-5p through mimic transfection significantly reduced POFUT1 transcript levels by approximately 46 % in HCT 116, 50 % in SW480, and 22 % in SW620 cells compared with controls. Dual-luciferase reporter assays confirmed direct binding of miR-642a-5p to two predicted sites within the POFUT1 3'UTR, resulting in a decrease of luciferase activity by 40-50 %. ConclusionThis study combines bioinformatics screening based on multiple linear regression and machine learning models, with experimental validation to identify miRNAs regulating POFUT1 expression in colon cancer. This integrative strategy allows the identification of a miRNA signature related to POFUT1 and provides novel insights into its post-transcriptional control. It may serve as a foundation for future diagnostic or therapeutic strategies in CRC.

cancer biology↗

bioRxiv2024

CXCL8 secreted by immature granulocytes inhibits wildtype hematopoiesis in chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy with limited therapeutic options. Single-cell analysis of clonal architecture demonstrated early clonal dominance with few residual wildtype hematopoietic stem cells. Circulating myeloid cells of the leukemic clone and the cytokines they produce generate a deleterious inflammatory climate. Our hypothesis is that therapeutic control of the inflammatory component in CMML could contribute to stepping down disease progression. The present study explores the contribution of immature granulocytes (iGRANs) to CMML progression. iGRANs can be detected and quantified in the peripheral blood of patients by spectral and conventional flow cytometry. Their accumulation is a potent and independent poor prognostic factor. These cells belong to the leukemic clone and behave as myeloid-derived suppressor cells. Bulk and single cell RNA sequencing revealed a pro-inflammatory status of iGRAN that secrete multiple cytokines of which CXCL8 at the highest level. This cytokine inhibits the proliferation of wildtype but not CMML hematopoietic stem and progenitor cells (HSPCs) in which CXCL8 receptors are epigenetically downregulated. CXCL8 receptor inhibitors and CXCL8 blockade restore wildtype HSPC proliferation, suggesting that relieving CXCL8 selective pressure on wildtype HSPCs is a potential strategy to slow CMML progression and restore some healthy hematopoiesis.

cancer biology↗

bioRxiv2022

The black goby Gobius niger Linnaeus, 1758 in the Marchica lagoon (Alboran Sea, Morocco): Ecological traits and site-related footprint

Fishes belonging to Gobiidae are well represented in the Marchica lagoon on the Moroccan Mediterranean coast, both in terms of species richness and abundance, with the black goby, Gobius niger Linnaeus, 1758, being the dominant species. The present study aims to examine (1) the spatial and temporal distribution of Gobius niger and its environmental drivers in the lagoon and (2) the potential lagoon-related footprint using morphometric, genetic and parasitological proxies. Systematic monthly sampling covering the whole lagoon basin performed between October 2015 and September 2016 revealed year-long presence of G. niger throughout the lagoon with significantly low densities in winter. The higher abundances were recorded in the shallow bottoms of the lagoon inner margins on a variety of substrates (mud, muddy-sand, sandy-mud and fine sand) mostly covered by macroalgae and/or seagrass meadows. Depth, that has to be seen as a variable that acts in concert with other factors such as temperature, vegetation cover and sediment as the Mean Grain Size, seems to be the most important predictor, explaining the distribution of G. niger in the lagoon, with a trend of increasing abundance towards shallower stations. Comparison of black goby populations from the Marchica lagoon with their counterparts from the adjacent Mediterranean coast of Morocco revealed that specimens caught at sea are of a bigger size compared to the lagoon population. Of the 180 gobies investigated, not a single one hosted the parasites we targeted in the parasitological approach, monogenean flatworms. The absence of population structuring, low genetic diversity and presence of common haplotypes indicate no apparent restriction in the gene flow between the two populations. Therefore, the observed morphometric differences seem to be due to the external environmental conditions rather than genetic differences. Gobius niger plays a key eco-trophic role by providing a link between benthic invertebrates and large predators. The shallow beds of the lagoon, where the species is abundant, are key habitats in the Marchica lagoon and need to be considered in all management plans aiming at the conservation of biodiversity and ecological processes.

ecology↗

bioRxiv2020

Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco

COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.

genomics↗