Biology subjects

Grabowska, A.

Publications and source records attributed to Grabowska, A..

4 recordsLinked to original sources

bioRxiv2024

Circular RNA - circCLIP2 is predominantly expressed in GSC niche and enhances glioblastoma aggressiveness via EMT and ECM signaling

Glioblastoma (GBM) is the most common and malignant type of brain tumor in adults and no effective therapies exist to combat this disease. Surgical resection, radio- and temozolomide-based-chemotherapy are insufficient mainly due to inter- and intra-tumoral heterogeneity of GBM tumors, therefore personalized approaches are required. Additionally, diverse tumor microenvironment with a leading role of glioblastoma stem cells (GSCs) in hypoxic core underlie the aggressiveness and recurrence of GBM. However, the molecules and pathways which directly promote tumor aggressiveness together with the driving process of epithelial-to-mesenchymal transition (EMT) and the components of extracellular matrix (ECM), remain only partially covered with prior studies focused mainly on coding oncogenes and tumor suppressor genes. Over the past years, a special attention has been paid to non-coding, circular RNAs (circRNAs) differentially expressed in various cancers, including GBM. Despite high abundance and stability, the exact biological roles of most individual circRNAs have not been fully revealed, so far. Besides anti-cancer targets, circRNAs have been considered as essential biomarkers and stratifying criterion of malignancy. Thus, studies on functions of differentially expressed circRNAs in GBM are an emerging field to be explored. In herein study, the biological role of circRNA CLIP2 (circCLIP2) was found highly overexpressed in primary tumor tissues. Upon the knock-down of circCLIP2 in 2D and 3D in vitro models, functional tests performed clearly indicate a significant contribution of circCLIP2 to aggressive potential of GBM as showed by decreased rates of proliferation, migration and invasion. Additional studies indicated predominant expression of circCLIP2 in GSC fractions additionally elevated by hypoxic conditions. The increased rates of proliferation and migration as well as molecular analyses were also confirmed in in vivo settings where xenograft model was applied. The expression of EMT marker Snail2 and ECM-degrading enzyme metalloproteinase 9 (MMP9) were significantly downregulated in the tumors formed from circCLIP2 silenced cells. Taken together, these results indicate a strong contribution of circCLIP2 in the aggressive phenotype of GBM which is due to a modulation of GSC proliferative potential as well as migration and invasion via EMT together with the modulator of ECM composition.

cancer biology↗

bioRxiv2024

Transcriptome-wide analysis of circRNA and RBP profiles and their molecular and clinical relevance for GBM

Glioblastoma (GBM) is the most aggressive and lethal type of glioma, characterized by aberrant expression of non-coding RNAs including circular RNAs (circRNAs). They might impact cellular processes by interacting with other molecules - like microRNAs or RNA-binding proteins (RBPs). The diagnostic value of circRNAs and circRNAs/RBPs complexes is still largely unknown. To explore circRNAs and RBPs transcripts expression in GBM, we performed and further analyzed RNA-seq data from GBM patients primary and recurrent tumor samples. We identified circRNAs differentially expressed in primary tumors, the circRNA progression markers in recurrent GBM samples as well as the expression profile of RBP transcripts. Subsequent analysis allowed us to generate a comprehensive catalog of circRNA-RBP interactions regarding both the RBPs sequestration by circRNA as well as the RBPs involvement in circRNA biogenesis. Furthermore, we demonstrated the clinical potential of circRNAs and RBPs in GBM and proposed them as the stratification markers in the de novo assembled tumor subtypes. Therefore, our transcriptome-wide study specified circRNA-RBP interactions that could play a significant regulatory role in gliomagenesis and GBM progression.

cancer biology↗

bioRxiv2020

PartSeg, a Tool for Quantitative Feature Extraction From 3D Microscopy Images for Dummies

BackgroundBioimaging techniques offer a robust tool for studying molecular pathways and morphological phenotypes of cell populations subjected to various conditions. As modern high resolution 3D microscopy provides access to an ever-increasing amount of high quality images, there arises a need for their analysis in an automated, unbiased and simple way. Segmentation of structures within cell nucleus, which is the focus of this paper, presents a new layer of complexity in the form of dense packing and significant signal overlap. At the same time the available segmentation tools provide a steep learning curve for new users with limited technical background. This is especially apparent in bulk processing of image sets, which requires the use of some form of programming notation. ResultsIn this paper, we present PartSeg, a tool for segmentation and reconstruction of 3D microscopy images, optimised for the study of cell nucleus. PartSeg integrates refined versions of several state-of-the-art algorithms, including a new multi-scale approach for segmentation and quantitative analysis of 3D microscopy images. The features and user-friendly interface of PartSeg were carefully planned with biologists in mind, based on analysis of multiple use cases and difficulties encountered with other tools, to offer ergonomic interface with a minimal entry barrier. Bulk processing in an ad-hoc manner is possible without the need for programmer support. As the size of datasets of interest grows, such bulk processing solutions become essential for proper statistical analysis of results. Advanced users can use PartSeg components as a library within Python data processing and visualisation pipelines, for example within Jupyter notebooks. The tool is extensible so that new functionality and algorithms can be added by the use of plugins. For biologists the utility of PartSeg is presented in several scenarios, showing the quantitative analysis of nuclear structures. ConclusionsIn this paper, we have presented PartSeg which is a tool for precise and verifiable segmentation and reconstruction of 3D microscopy images. PartSeg is optimised for cell nucleus analysis and offers multiscale segmentation algorithms best-suited for this task. PartSeg can also be used for bulk processing of multiple images and its components can be reused in other systems or computational experiments. Contact g.bokota@cent.uw.edu.pl, a.magalska@nencki.edu.pl, d.plewczynski@cent.uw.edu.pl

bioinformatics↗

bioRxiv2019

Dissociable brain mechanisms for long-term memory of disgust- and fear- related associations

Remembering events that evoke emotions such as disgust or fear is critical to our survival. However, previous studies investigating the interplay between emotion and memory disregarded the effects of specific emotions, leading to inconsistent results. Also, the role of amygdala throughout memory stages has been poorly understood. Here, we show that after 3 weeks delay, word pairs evoking disgust were remembered better than pairs evoking fear. These two emotions distinctly modulated neural mechanisms of memory. Successful encoding of disgust-evoking information was mediated by univariate activation in amygdala and perirhinal cortex, in contrast to fear-evoking memories that engaged hippocampus and parahippocampal gyrus. Critically, univariate activation in the amygdala during encoding was correlated with memory reinstatement of individual word pairs, and more so for disgust than for fear. Together, these findings shed a new light on the role of the amygdala and medial temporal lobe regions in encoding and reinstatement of specific emotional memories.

neuroscience↗