Bioinformatics analysis of the ribosomal protein, Rpl27, Rpl37a and Rpl41:3-D protein modeling and protein-protein interaction prediction

Ribosomal proteins (RP) are constituents of ribosome that is important in protein biosynthesis and likely to have extraribosomal functions. Many RPs are related to various diseases and cancers. From previous studies, RPL27, RPL37a and RPL41 gene were reportedly downregulated in all cell lines derived from Nasopharyngeal Carcinoma (NPC) tissues compared to the normal counterpart. Thus, present study aimed to understand the three genes in protein level and its interaction with other proteins. The methods used RPL27, RPL37a and RPL41 3-D (3-Dimension) protein models to search for structural neighbor in predicting protein-protein interaction. Subsequently, the structural neighbors and their partners were docked to predict functions. As a result, RPL27 revealed interaction with SYNJ2 and UBC9 in dock complex. RPL27 was predicted to mediate RNA binding protein and deregulate sumoylation. Additionally, RPL37a interacted with CTNNBI, SCMH I and ATBFI. RPL37a was predicted to deregulate Wnt degradation pathway and inhibit~­ C8tenin migration. RPL37a might also regulate homeotic transcription. Further studies such as alanine scanning mutagenesis can provide deeper insight on protein recognition mechanism and identification of hot spots for protein kinetic studies

Human Ribosomal Proteins RPeL27, RPeL43 and RPeL41 are Up-regulated in Nasopharyngeal Carcinoma Cell Lines

Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes’ involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41 and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semi-quantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than down-regulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41 and RPeL43 as potential markers of NPC, and provide insights into the interaction targets of RPeL27 and RPeL43 proteins

Predicted interaction of human Ribosomal Protein S15 with Fragile X Mental Retardation Protein

In addition to the central role of ribosome biogenesis, the human ribosomal protein S15 (RPS15) has extra-ribosomal roles that include its association with a congenital disease and a few types of cancer. However, current knowledge of its functions in the context of extra-ribosomal activities remains fragmented. An approach to gain insights into the interaction between RPS15 and possible protein partners is via Bioinformatics strategies. Based on the sequence-to-structure-to-function paradigm, structural data of a protein can be computationally analysed to derive logical interacting partners. This method can include three-dimensional model construction, structural neighbour prediction, and molecular docking analysis. By using this approach, we have constructed RPS15 3D-structural models that have allowed the prediction of 23 structural neighbours. Of these, two that are from human origin were further analysed and only one have logical prospect of binary protein-protein interactions. Further analysis of this structural neighbour revealed 7 candidate docking partners. From these, our molecular docking analysis demonstrated two most logical dock models of interactions between RPS15 with two different domains of the Fragile X Mental Retardation Protein 1 (FMRP1) protein. Hence, we have provided in silico evidence of de novo protein-protein interaction between RPS15 and the Fragile X Mental Retardation Protein 1 (FMRP1)

Selective Differential Expression Of The Ribosomal Protein Genes El14 And Us19 In A Well-Differentiated Epithelial Cell Line Of Nasopharyngeal Carcinoma

Besides ribosome biogenesis and protein synthesis, ribosomal proteins (RP) are associated with congenital diseases and cancers. A small subset of ribosomal protein genes has shown expression pattern indicative of their association with nasopharyngeal carcinoma (NPC). Nevertheless, the list of RP genes that are NPC-associated factors is largely incomplete. Herein we report the expression patterns of eL14 and uS19 in NPC normal nasopharyngeal epithelium cell lines. Expression levels of eL14 and uS19 in the NPC-HK1 cell line was comparatively analysed with a normal nasopharyngeal cell line (NP69) using Reverse Transcription – Polymerase Chain Reaction (RT-PCR). We revealed that the transcript level of eL14 was significantly down-regulated in HK1 when compared to NP69. The expression behaviour of eL14 is demonstrated for the first time in the NPC context. In contrast, the transcript level of uS19 was up-regulated in NPC/HK1 compared to NP69, but not to a statistically significant extent. This study provides new evidence of differential expression of the ribosomal protein gene, eL14 in an NPC cell line derived from well-differentiated squamous cell carcinoma of human nasopharynx. It adds to the list of NPC-associated ribosomal protein genes amenable for development of biomarkers for improved molecular diagnosis of nasopharyngeal cancer

A Numerical Study of Phase Transitions Inside the Pores of Aerogels

Phase transitions inside the pores of an aerogel are investigated by modelizing the aerogel structure by diffusion-limited cluster-cluster aggregation on a cubic lattice in a finite box and considering $q$-states Potts variables on the empty sites interacting via nearest-neighbours. Using a finite size scaling analysing of Monte-Carlo numerical results, it is concluded that for $q=4$ the transition changes from first order to second order as the aerogel concentration (density) increases. Comparison is made with the case $q=3$ (where the first order transition is weaker in three dimensions) and with the case $q=4$ but for randomly (non correlated) occupied sites. Possible applications to experiments are discussed.Comment: RevTex, 12 pages + 10 postscript figures compressed using "uufiles", To appear in J. of Non-Cryst. Solid

Renal screening in children after exposure to low dose melamine in Hong Kong: cross sectional study

Objective To investigate the renal outcomes of children after exposure to low dose melamine in Hong Kong

Lupus nephritis in Chinese children--a territory-wide cohort study in Hong Kong

We report a multicenter study of Chinese children in Hong Kong with systemic lupus erythematosus (SLE) nephritis. Children were included if: they fulfilled the ACR criteria, had significant proteinuria or casturia, were Chinese and younger than 19 years and had been diagnosed with SLE between January 1990 and December 2003. Investigators in each center retrieved data on clinical features, biopsy reports, treatment and outcome of these patients. There were 128 patients (eight boys, 120 girls; mean age: 11.9+/-2.8 years). About 50% presented with multisystem illness and 40% with nephritic/nephrotic symptoms. Negative anti-dsDNA antibodies were found in 6% of the patients. Renal biopsy revealed WHO Class II, III, IV and V nephritis in 13 (10%), 22 (17%), 69 (54%) and 13 (10%) patients, respectively. The clinical severity of the nephritis did not accurately predict renal biopsy findings. The follow-up period ranged from 1 to 16.5 years (mean+/-SD: 5.76+/-3.61 years). During the study five patients died (two from lupus flare, one from cardiomyopathy, two from infections). Four patients had endstage renal failure (ESRF) (one died during a lupus flare). All deaths and end-stage renal failure occurred in the Class IV nephritis group. Chronic organ damage was infrequent in the survivors. The actuarial patient survival rates at 5, 10 and 15 years of age were 95.3, 91.8, and 91.8%, respectively. For Class IV nephritis patients, the survival rates without ESRF at 5, 10, and 15 years were 91.5, 82.3 and 76%, respectively. The survival and chronic morbidity rates of the Chinese SLE children in the present study are comparable to those of other published studies.postprin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin