Biology subjects

Meena, D.

Publications and source records attributed to Meena, D..

5 recordsLinked to original sources

bioRxiv2025

NLRP3 Inflammasome Exhibits Context-Dependent Roles in Glioblastoma-Astrocyte Crosstalk

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by molecular and cellular heterogeneity and poor patient survival. NLRP3 inflammasome regulates inflammation and cell death with context-specific roles in cancer, but its functions in GBM tumour and astrocyte interactions remain unclear. In this study, we analyzed NLRP3 expression and function in GBM cell lines (LN-229 and LN18), astrocytes (SVG), patient-derived tissues, and organoids. Basal NLRP3 expression was higher in astrocytes than in GBM cells and increased after LPS stimulation, altering astrocyte morphology and NLRP3 subcellular localization. siRNA-mediated silencing of NLRP3 reduced GBM proliferation, migration, and viability in GBM cells, while enhancing proliferation and cytokine secretion in astrocytes, highlighting its context-dependent effects. NLRP3 deficiency exhibited reciprocal cytokine paracrine signaling, with GBM cells releasing elevated levels of IL-6 and TNF-, and astrocytes releasing elevated levels of IL-1{beta}. Glyburide treatment reduced NLRP3 expression and IL-1{beta} release in GBM cells but elevated NLRP3 and IL-1{beta} in astrocytes. Overall, these data reveal NLRP3s dual roles in GBM-astrocyte crosstalk, suggesting cell-type-selective inhibition for therapeutic exploration.

cancer biology↗

bioRxiv2025

NLRP12-mediated Glioblastoma-Astrocyte Cross-talk Promotes Tumor Growth

Nucleotide-binding domain leucine-rich repeat-containing receptors (NLR) are cytosolic pattern recognition receptors that regulate inflammation by sensing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). NLRP12 is a cytosolic protein with inflammation-promoting and inflammation-attenuating properties. NLRP12 exhibits tumor-suppressive or tumor-promoting effects that may be cancer, cell-type, context-dependent, aided by differences in the microenvironment contributing to the pathophysiology of hepatocellular carcinoma, prostate cancer, colitis-associated cancer, and glioblastoma (GBM). GBM is a grade IV malignant brain tumor with poor patient survival and high tumor recurrence due to a heterogeneous cell population and angiogenesis. Our previous research reported NLRP12 as a potential prognostic marker for GBM with high expression in GBM patient tissues. In the present study, we investigated the role of NLRP12-mediated signalling between GBM and tumor-adjacent astrocytes, using a comprehensive panel of experimental models, including LN-229 GBM and SVG astrocyte cell lines, cell line-derived spheroids, patient-derived primary glioma cells, and patient-derived glioma organoids. We report that NLRP12 deficiency reduces cell proliferation and viability in the LN-229 cells, but increases these parameters in SVG cells. Furthermore, NLRP12-deficient LN-229 cells display attenuated ability to form three-dimensional spheroids, indicating a role of NLRP12 in anchorage-independent growth, which is considered a hallmark of tumorigenicity. Analysis of patient-derived glioma tissue and patient-derived GBM organoids revealed differential expression of NLRP12. Our findings suggest that NLRP12 modulates GBM cell proliferation, viability, and anchorage-independent growth in a cell-context dependent manner. The cell-type-specific roles of NLRP12 may underlie its complex contribution to GBM pathophysiology with implications for therapy and prognosis. SummaryNLRP12, a cytosolic regulator of inflammation, exhibits context-dependent roles in cancer. Its deficiency reduces glioblastoma cell proliferation, viability, and spheroid formation, while enhancing these properties in astrocytes, indicating a cell-type-dependent role for NLRP12 in GBM progression.

cancer biology↗

bioRxiv2025

Repurposing Nelfinavir: AIM2 Inflammasome-Driven Anti-tumor Effects in Glioblastoma

Nelfinavir (NFR), originally developed as an antiretroviral agent for the human immunodeficiency virus, has demonstrated anti-cancer properties across various malignancies; however, its therapeutic potential in Glioblastoma (GBM) remains largely unexplored. In the present study, we investigated the anti-tumor effects of NFR in GBM using a comprehensive panel of experimental models, including established GBM cell lines, GBM cell line-derived spheroids, patient-derived primary glioma cells, and patient-derived glioma organoids. We further evaluated the synergistic potential of NFR in combination with standard chemotherapeutic agents, Carboplatin and Doxorubicin, across these platforms. In vitro analyses revealed that NFR significantly inhibits GBM cell proliferation and induces both apoptotic and necrotic cell death. Mechanistically, we identified activation of the AIM2 inflammasome as a potential additional pathway mediating the anti-tumor effects of NFR. Collectively, our findings highlight NFR as a promising therapeutic candidate for GBM, exerting its effects through anti-proliferative and pro-death mechanisms potentially linked to AIM2 inflammasome activation.

cancer biology↗

bioRxiv2024

Innate Immune Receptor NLRX1: Potential Modulator of Glioblastoma Pathophysiology

Gliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immune pattern recognition receptor that exhibits tumor-suppressive and tumor-promoting effects that may be cancer or cell-type, context-dependent, aided by differences in the microenvironment. Here, we report that NLRX1 is differentially expressed in microglia, astrocytes, GBM cell lines, and glioma patient tissues. siRNA-mediated silencing of Nlrx1 decreases the ability of the GBM cell line, LN-229, to proliferate and migrate. Nlrx1-/- GBM cells exhibit attenuated ability to generate 3D spheroids and enhanced capability to form tunneling nanotubes. Moreover, Nlrx1-/- GBM cells show decreased expression of autophagy markers, suggesting that NLRX1 plays a role in maintaining autophagy in GBM. In summary, our findings indicate that NLRX1 may modulate GBM pathophysiology by regulating GBM cell proliferation, migration, and metabolism. We believe our understanding of NLRX1 in GBM pathophysiology paves the potential development of GBM-targeting therapeutics that may delay disease progression and/or improve survival.

cancer biology↗

bioRxiv2017

The genetics of the human face: identification of large effect single gene variants

In order to discover specific variants with relatively large effects on the human face we have devised an approach to identifying facial features with high heritability. This is based on using twin data to estimate the additive genetic value of each point on a face, as provided by a 3D camera system. In addition, we have used the ethnic difference between East Asian and European faces as a further source of face genetic variation. We use principal components analysis to provide a fine definition of the surface features of human faces around the eyes and of the profile, and chose upper and lower 10% extremes of the most heritable PCs for looking for genetic associations. Using this strategy for the analysis of 3D images of 1832 unique volunteers from the well characterised People of the British Isles study [1, 2] and 1567 unique twin images from the TwinsUK cohort (www.twinsuk.ac.uk), together with genetic data for 500,000 SNPs, we have identified three specific genetic variants with notable effects on facial profiles and eyes.\n\nSignificance statementThe human face is extraordinarily variable and the extreme similarity of the faces of identical twins indicates that most of this variability is genetically determined. This level of genetic variability has probably arisen through natural selection, for example, for recognition of membership of a group or as a consequence of differential mate selection with respect to facial features. We have devised an approach to identifying specific genetic effects on particular facial features. This should enable the understanding, eventually at the molecular level, of the nature of this extraordinary genetic variability, which is such an important feature of our everyday human interactions.\n\nAuthor ContributionsWFB conceived the project. BW and TD organised collection of PoBI data and KH, DJMC, DM, AB and WFB assisted in data collection. TDS, PH and AN collected TwinsUK data. WPK and WJC conducted image registration analysis under supervision of JK. DJMC analysed registered image data and genetic data under supervision of WFB. WFB and DJMC wrote the manuscript, with WJC and WPK contributing additional technical material. WFB and BW supervised the project.

genetics↗