Biology subjects

Revanth, M.

Publications and source records attributed to Revanth, M..

3 recordsLinked to original sources

bioRxiv2026

Genetic and structural interpretation of NLRP1 FIIND domain variants in glioma in an Indian cohort: a pilot study

Gliomas, particularly glioblastoma (GBM), are aggressive primary brain tumors associated with dysregulated NLR signaling, a pathway central to innate immunity and inflammation. NLRP1 triggers proinflammatory cytokine release and pyroptotic cell death via autoproteolytic cleavage. The FIIND missense variant rs11651270 (M1184V) may modulate this cleavage process. While NLRP1 polymorphisms are associated with various diseases and cancers, their specific impact on glioma remains to be investigated. In our study, five FIIND-domain single-nucleotide polymorphisms (SNPs) of NLRP1 rs371579423, rs58604457, rs57636751, rs11651270, and rs2301583, were investigated by Sanger sequencing in a clinical cohort of glioma patients and compared against population-matched controls from the GenomeIndia dataset (Rajasthan cohort) using genetic association models. Molecular dynamics simulations were performed to evaluate the structural effects of the missense variant rs11651270 (M1184V) in NLRP1 during pre- and post-cleavage states. The linked variants rs58604457 (G>A) and rs57636751 (C>T) exhibited complete linkage disequilibrium (r2=1.00) and were significantly associated with lower odds of glioma (odds ratio ~0.5). The missense variant rs11651270 (T>C) showed no association with glioma risk. Notably, the SNP rs2301583 had a higher allelic frequency in glioma cases despite being absent in the GenomeIndia population-based control catalogue. Molecular dynamics simulations revealed that the M1184V substitution stabilizes local FIIND architecture by preserving {beta}-strand organization through persistent interactions with neighboring residues. This study provides the first combined genetic and structural analysis of NLRP1 FIIND-domain variants in an Indian glioma cohort. These findings illustrate the potential value of integrating population-based genetic association with structural modelling to generate hypotheses and uncover potential functional mechanisms of inflammasome-gene variants in neuro-oncology.

cancer biology↗

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↗