Biology subjects

Karlik, A.

Publications and source records attributed to Karlik, A..

3 recordsLinked to original sources

bioRxiv2025

ANDROGENS PROTECT ILC2S FROM FUNCTIONAL SUPPRESSION DURING INFLUENZA VIRUS INFECTION

Biological sex differences in morbidity upon influenza A virus (IAV) infection are linked to stronger IFN-centered immune responses in females, yet the regulatory role of sex hormone receptors in immune cell subsets is incompletely understood. Lung-resident group 2 innate lymphoid cells (ILC2s) express notably high levels of androgen receptors (AR). In IAV infection, ILC2s produce type 2 cytokines and facilitate tissue repair, but they also may be functionally suppressed by type 1 cytokines. Here we report sex differences in the magnitude of lung ILC2 functional suppression at the peak of sublethal IAV infection. Relative to males, ILC2s in females show attenuated proliferation, decreased propensity for IL-5 and amphiregulin production and reduced expression of GATA3 and IL-33R, features supported by divergent transcriptomes. Equivalent inflammatory cytokine levels and viral load suggested sex differences in ILC2-intrinsic factors. Indeed, naive female ILC2s showed elevated IFNGR expression and higher phospho-STAT1 levels following IFN{gamma} stimulation, and lymphocyte-restricted STAT1 deficiency reversed IAV-induced suppression of female ILC2s. Lymphocyte-restricted AR deficiency or loss of androgens via orchiectomy led to increased IFNGR expression and suppression of male ILC2s. These data support the hypothesis that intrinsic AR activity regulates IFNGR-STAT1 signaling pathways to preserve canonical ILC2 function in males during IAV infection.

immunology↗

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↗

bioRxiv2019

DRB1 as a mediator between transcription and microRNA processing

DRB1 (HYL1) is a double-stranded RNA binding protein involved in miRNA processing in plants. It is a core component of the Microprocessor complex and enhances the efficiency and precision of miRNA processing by DCL1 protein. In this work, we report a novel function of DRB1 protein in the transcription of MIR genes. DRB1 co-localizes with RNA Polymerase II and affects its distribution along MIR genes. Moreover, proteomic experiments revealed that DRB1 protein interacts with many transcription factors. Finally, we show that the action of DRB1 is not limited to MIR genes as it impacts expression of many other genes, majority of which are involved in plant response to light. These discoveries add DRB1 as another player of gene regulation at transcriptional level, independent of its role in miRNA biogenesis.

plant biology↗