Biology subjects

Rao, M. K.

Publications and source records attributed to Rao, M. K..

4 recordsLinked to original sources

bioRxiv2026

Midkine Dependency Defines a Therapeutically Actionable Vulnerability in Medulloblastoma

Medulloblastoma (MB), the most common malignant pediatric brain tumor, remains associated with high recurrence rates and substantial treatment-related morbidity despite aggressive multimodal therapy. Here, we identify midkine (MDK), a secreted growth factor/cytokine, as a previously unrecognized central regulator of MB growth and survival. Tissue microarray analysis revealed elevated MDK protein expression in MB specimens, and single-cell RNA sequencing datasets showed tumor cell-specific MDK expression. Genetic depletion or antibody-mediated neutralization of MDK suppressed proliferation and survival and induced apoptosis across multiple MB cell lines, whereas recombinant MDK supplementation exerted the opposite effect. Mechanistically, phosphokinase profiling and immunoblot analyses showed that MDK signals through multiple receptors, including nucleolin (NCL), LRP1, and syndecan-2 (SDC2), to sustain oncogenic ERK1/2 and Akt-mTOR-S6 signaling. Transcriptomic profiling following MDK silencing or depletion revealed marked suppression of ribosome biogenesis, global protein translation, and MYC-driven programs, coupled with activation of inflammatory and apoptotic responses. Consistently, mechanistic studies utilizing RPS6 staining, ribosomal RNA quantification, puromycin SUnSET, and OPP incorporation assays confirmed that loss of MDK impairs ribosome biogenesis and protein synthesis. Notably, MDK suppression also triggered robust activation of the IFN-cGAS-STING pathway, linking translational stress to innate immune signaling. In orthotopic xenograft models, CRISPR-mediated MDK knockout significantly reduced tumor growth and prolonged survival. Together, these findings establish MDK as a key integrator of oncogenic signaling, translational control, and innate immunity in MB, highlighting MDK as a compelling therapeutic target.

cancer biology↗

bioRxiv2025

From Nutraceutical to Molecular Targets: Antidiabetic Effects of Spirulina maxima Validated by In Vivo and In Silico Studies.

BackgroundSpirulina maxima is a cyanobacterium, which has been a staple food in Mexico since 16th century. Presently this nutraceutical alga has been explored for its antioxidant, anticancer, hepatoprotective and antilipemic properties. The present study is focused on the antihyperglycemic effect of S.maxima in streptozotocin induced diabetes mellitus. The molecular characterization of S. maxima and the anti-diabetic targets are deduced from in-silico analysis. MethodsThe anti-hyperglycemic potential of S. maxima was evaluated in male Wistar rats injected with streptozotocin (45 mg/kg (i.p)). The Animals were grouped based on the blood levels into Normal control (n=6); Normal control administered with S. maxima (n=6), Diabetic control, Diabetic group treated with S. maxima(n=6),, the diabetic group treated with Glibenclamide (600{micro}g/kg b.w.) (n=6), S. maxima (500mg/kg) was administrated orally for 15 days, and the variations in blood glucose levels along with the lipid levels and the antioxidant status were determined.The lipids content of S. maxima was characterized through GCMS. The lipids identified were docked in-silico with AMPK molecule and PPAR{gamma}, potential targets for antidiabetic drugs. Results and conclusionsS. maxima administration in diabetic rats significantly reduced the blood glucose levels by 62.76% while the cholesterol, triglycerides, and VLDL level were marginally reduced. The HDL levels were significantly enhanced by 32.4%. The antioxidant markers such as catalase, SOD and GSH levels, were elevated by 13.8, 25 and 7.47%. The TBARS levels were reduced up to 15.1%. The functional group analysis showed characteristic vibrations of polysaccharides proteins, lipids and aromatic compounds. The GCMS characterization of S. maxima showed the presence of C8, C9 and C13 lipids at a concentration less than 1% of total lipids, while C5, C11, C16 and C20 lipids were 1-10% of total lipid content while C6, C10, C15 and C22 lipids were above 10% of total lipids. The docking results revealed the binding affinity of C5, C6, C10, C11 and C18 with regulatory gamma subunit of AMPK while C5, C6 and C11 lipids had the binding affinity with PPAR-{gamma} receptor. The study revealed, the antidiabetic potential of S. maxima, and hypothesized AMPK and PPAR-{gamma} as a potential target in maintaining blood glucose homeostasis.

biochemistry↗

bioRxiv2023

Nucleoporin93 (Nup93) Limits Yap Activity to Prevent Endothelial Cell Senescence

Endothelial cells (ECs) form the innermost lining of the vasculature and serve a pivotal role in preventing age-related vascular disease. Endothelial health relies on the proper nucleocytoplasmic shuttling of transcription factors via nuclear pore complexes (NPCs). Emerging studies report NPC degradation with natural aging, suggesting impaired nucleocytoplasmic transport in age-related EC dysfunction. We herein identify nucleoporin93 (Nup93), a crucial structural NPC protein, as an indispensable player for vascular protection. Endothelial Nup93 protein levels are significantly reduced in the vasculature of aged mice, paralleling observations of Nup93 loss when using in vitro models of endothelial aging. Mechanistically, we find that loss of Nup93 impairs NPC transport, leading to the nuclear accumulation of Yap and downstream inflammation. Collectively, our findings indicate maintenance of endothelial Nup93 as a key determinant of EC health, where aging targets endothelial Nup93 levels to impair NPC function as a novel mechanism for EC senescence and vascular aging.

physiology↗

bioRxiv2022

RNA binding to human METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro

Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino group of adenosine bases in RNA (m6A) and DNA (m6dA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear. By systematically studying methylation activity and binding affinity to a number of DNA and RNA oligos with different propensities to form inter- or intra-molecular duplexes or single-stranded molecules in vitro, we uncover an inverse relationship for substrate binding and methylation and show that METTL3-METTL14 preferentially catalyzes the formation of m6dA in single-stranded DNA (ssDNA), despite weaker binding affinity to DNA. In contrast, it binds structured RNAs with high affinity, but methylates the target adenosine in RNA (m6A) much less efficiently than it does in ssDNA. We also show that METTL3-METTL14-mediated methylation of DNA is largely regulated by structured RNA elements prevalent in long noncoding and other cellular RNAs.

biochemistry↗