Computational Biology - Publications
Permanent URI for this collection
Browse
Recent Submissions
1 - 5 of 147
-
ItemSirtuin 7 Promotes Mesenchymal to Epithelial Transition by β-Catenin Redistribution and Stabilization( 2020-06-23)SIRT7 belongs to the family of “NAD+ dependent deacetylases” called Sirtuins. In the present work we report a novel role of SIRT7 in regulating cellular polarity. SIRT7 overexpression in immortalized mouse fibroblasts (NIH3T3) induced epithelial transition. This transition was accompanied by typical N- to E- cadherin transition, stabilization of β-catenin, and the downregulation of transcription factors responsible for maintenance of mesenchymal phenotype (Snail, Slug, and Zeb1). Interestingly, a subpopulation of cells overexpressing SIRT7 exhibited an intermediate stage between mesenchymal and epithelial characters. Transformed epithelial cells showed a loss of heterochromatisation as evidenced by a loss of HP1α and H3K9 dimethylation staining. In conclusion, we report a role of SIRT7 in mesenchymal cells, which may have implications for health and disease.
-
ItemLong noncoding RNA DRAIC inhibits prostate cancer progression by interacting with IKK to inhibit NF-κB activation( 2020-03-01)DRAICis a 1.7 kbspliced long noncoding RNA downregulated in castration-resistant advanced prostate cancer. Decreased DRAIC expression predicts poor patient outcome in prostate and seven other cancers, while increased DRAIC represses growth of xeno-grafted tumors. Here, we show that cancers with decreased DRAIC expression have increased NF-κB target gene expression. DRAIC downregulation increased cell invasion and soft agar colony formation; this was dependent on NF-κB activation. DRAIC interacted with subunits of the IκB kinase (IKK) complex to inhibit their interaction with each other, the phosphorylation of IκBα, and the activation of NF-κB. These functions of DRAIC mapped to the same fragment containing bases 701-905. Thus, DRAIC lncRNA inhibits prostate cancer progression through suppression of NF-κB activation by interfering with IKK activity. Significance: A cytoplasmic tumor-suppressive lncRNA interacts with and inhibits a major kinase that activates an oncogenic transcription factor in prostate cancer.
-
ItemIdentifying the mechanisms of α-synuclein-mediated cytotoxicity in Parkinson's disease: New insights from a bioinformatics-based approach( 2020-08-01)Aim: A large body of evidence has implicated the cytotoxicity of α-synuclein in Parkinson's disease (PD). We planned to use a bioinformatics-based approach to gain further insight into this process. Materials & methods: Using STRING version 10, we identified interacting proteins of α-synuclein. Using α-synuclein and one of these interactors involved in apoptosis as query proteins, we identified other linked proteins. We further analyzed the interactions between some of these proteins by Protein-Protein Docking using ClusPro. Results: We identified BAX as an interacting protein of α-synuclein. Interactions of α-synuclein and BAX as well as BAX and BCL2L1 were determined. Conclusion: The interaction of α-synuclein and BAX could play a crucial role in the cell death process of PD where apoptosis and mitochondrial permeability transition-driven necrosis may coexist.
-
ItemRapamycin alternatively modifies mitochondrial dynamics in dendritic cells to reduce kidney ischemic reperfusion injury( 2021-05-02)Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with rapamycin (10 ng/mL) for 1 h before LPS. In contrast, rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of rapamycin-treated DCs to WT recipients 24 h before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/mL) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.
-
ItemExosomes: Insights from retinoblastoma and other eye cancers( 2020-10-01)Exosomes, considered as cell debris or garbage bags, have been later characterized as nanometer-sized extracellular double-membrane lipid bilayer bio-vesicles secreted by the fusion of vesicular bodies with the plasma membrane. The constituents and the rate of exosomes formation differ in different pathophysiological conditions. Exosomes are also observed and studied in different parts of the eye, like the retina, cornea, aqueous, and vitreous humor. Tear fluid consists of exosomes that are shown to regulate various cellular processes. The role of exosomes in eye cancers, especially retinoblastoma (RB), is not well explored, although few studies point towards their presence. Retinoblastoma is an intraocular tumor that constitutes 3% of cases of cancer in children. Diagnosis of RB may require invasive procedures, which might lead to the spread of the disease to other parts. Due to this reason, better ways of diagnosis are being explored. Studies on the exosomes in RB tumors and serum might help designing better diagnostic approaches for RB. In this article, we reviewed studies on exosomes in the eye, with a special emphasis on RB. We also reviewed miRNAs expressed in RB tumor, serum, and cell lines and analyzed the targets of these miRNAs from the proteins identified in the RB tumor exosomes. hsa-miR-494 and hsa-miR-9, upregulated and downregulated, respectively in RB, have the maximum number of targets. Although oppositely regulated, they share the same targets in the proteins identified in RB tumor exosomes. Overall this review provides the up-to-date progress in the area of eye exosome research, with an emphasis on RB.