Biology subjects

Janu, V.

Publications and source records attributed to Janu, V..

3 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↗

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↗