scholarly journals Predicting Relative Protein Abundance via Sequence-Based Information

2021 ◽  
Author(s):  
Gregory Parkes ◽  
Rob M Ewing ◽  
Mahesan Niranjan
Keyword(s):  
Cell Lines ◽  
Significant Proportion ◽  
Protein Abundance ◽  
Mrna Levels ◽  
Biological Processes ◽  
Cellular Mechanisms ◽  
Regulatory Processes ◽  
Complex Interactions ◽  
Health And Disease ◽  
Multiple Cell

Understanding the complex interactions between transcriptome and proteome is essential in uncovering cellular mechanisms both in health and disease contexts. The limited correlations between corresponding transcript and protein abundance suggest that regulatory processes tightly govern information flow surrounding transcription and translation, and beyond. In this study we adopt an approach which expands the feature scope that models the human proteome: we develop machine learning models that incorporate sequence-derived features (SDFs), sometimes in conjunction with corresponding mRNA levels. We develop a large resource of sequence-derived features which cover a significant proportion of the H. sapiens proteome, demonstrate which of these features are significant in prediction on multiple cell lines, and suggest insights into which biological processes can be explained using these features. We reveal that (a) SDFs are significantly better at protein abundance prediction across multiple cell lines both in steady-state and dynamic contexts, (b) that SDFs can cover the domain of translation with relative efficiency but struggle with cell-line specific pathways and (c) provide a resource which can be plugged into many subsequent protein-centric analyses.

Increased expression of the glioma-associated antigen ARF4L after loss of the tumor suppressor PTEN

2008 ◽  
Vol 108 (2) ◽  
pp. 299-303 ◽  
Author(s):  
John H. Chi ◽  
Amith Panner ◽  
Kristine Cachola ◽  
Courtney A. Crane ◽  
Joseph Murray ◽  
...  
Keyword(s):  
Cell Lines ◽  
Blot Analysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Adenosine Diphosphate ◽  
Cellular Mechanisms ◽  
Tumor Associated Antigens ◽  
Protein Levels ◽  
Multiple Cell ◽  
Specific Antigens ◽  
The Relationship

Object Despite recent advances in cancer immunotherapy, cellular mechanisms controlling expression of tumor-associated antigens are poorly understood. Mutations in cancer cells, such as loss of PTEN, may increase expression of tumor-associated antigens. The authors investigated the relationship between PTEN status and the expression of a glioma-associated antigen, adenosine diphosphate–ribosylation factor 4–like (ARF4L) protein. Methods Human glioma cell lines with confirmed PTEN status were examined by Northern blot analysis and quantitative polymerase chain reaction. Western blot analysis was used to measure ARF4L protein levels across multiple cell lines. Results The loss of PTEN was shown to lead to increased levels of ARF4L protein but no change in transcript levels. Cell lines with serial mutations, including activation of Ras and Akt pathways, also demonstrated increased levels of ARF4L protein, which decreased after treatment with rapamycin. The ARF4L transcript preferentially localized to the polysomal compartment after PTEN loss in glioma or activation of Akt in human astrocytes. Conclusions Expression of ARF4L is controlled by the activated Akt/mTOR pathway, which is a downstream effect of the loss of PTEN function. Mutations leading to oncogenesis may impact the regulation and expression of tumor specific antigens. Screening of mutation status in glioma may be helpful in selecting patients for immunotherapy trials in the future.

scholarly journals Periodontal cell mechanotransduction

Open Biology ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 180053 ◽  
Author(s):  
Sasanka S. Chukkapalli ◽  
Tanmay P. Lele
Keyword(s):  
Stem Cells ◽  
Epithelial Cells ◽  
Periodontal Disease ◽  
Significant Role ◽  
Cell Types ◽  
Mechanical Stresses ◽  
Mechanical Forces ◽  
Biological Processes ◽  
Cellular Mechanisms ◽  
Health And Disease

The periodontium is a structurally and functionally complex tissue that facilitates the anchorage of teeth in jaws. The periodontium consists of various cell types including stem cells, fibroblasts and epithelial cells. Cells of the periodontium are constantly exposed to mechanical stresses generated by biological processes such as the chewing motions of teeth, by flows generated by tongue motions and by forces generated by implants. Mechanical stresses modulate the function of cells in the periodontium, and may play a significant role in the development of periodontal disease. Here, we review the literature on the effect of mechanical forces on periodontal cells in health and disease with an emphasis on molecular and cellular mechanisms.

Differentiation, cancer, and anticancer activity

1988 ◽  
Vol 66 (6) ◽  
pp. 478-489 ◽  
Author(s):  
Chin-Yuan Tzen ◽  
David N. Estervig ◽  
Parviz Minoo ◽  
Michiko Filipak ◽  
Peter B. Maercklein ◽  
...  
Keyword(s):  
Integrated Control ◽  
Biological Processes ◽  
Cellular Mechanisms ◽  
Regulatory Processes ◽  
Proliferation And Differentiation ◽  
Multistep Process ◽  
Stems Cells ◽  
Distinct Sequence ◽  
One Step ◽  
Differentiation And Proliferation

Carcinogenesis is a multistep process that results from the development of a variety of defects in the control of differentiation and proliferation. To investigate this concept further, 3T3 T mesenchymal stems cells were employed to establish that a distinct sequence of biological processes is involved in the control of differentiation and proliferation, and that these processes are integrally regulated. Specific defects in these regulatory processes were next established as being involved in carcinogenesis. These defects, however, were found not to be absolute; rather, they appear to involve changes in the stringency by which differentiation and proliferation are integrally regulated. Finally, it was established that when normal or transformed stem cells are induced to undergo nonterminal differentiation (which is one step in the integrated control of proliferation and differentiation), they can be made resistant to carcinogenesis or to revert to a nontransformed state. These data provide strong evidence that a critically important requirement for normal homeostasis is maintenance of intact cellular mechanisms to integrally regulate differentiation and proliferation.

scholarly journals An integrated landscape of protein expression in human cancer

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Andrew F. Jarnuczak ◽  
Hanna Najgebauer ◽  
Mitra Barzine ◽  
Deepti J. Kundu ◽  
Fatemeh Ghavidel ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protein Abundance ◽  
Sample Type ◽  
Mrna Levels ◽  
Poor Predictor ◽  
Median Correlation ◽  
Expression Atlas ◽  
Transcriptomics Data

AbstractUsing 11 proteomics datasets, mostly available through the PRIDE database, we assembled a reference expression map for 191 cancer cell lines and 246 clinical tumour samples, across 13 lineages. We found unique peptides identified only in tumour samples despite a much higher coverage in cell lines. These were mainly mapped to proteins related to regulation of signalling receptor activity. Correlations between baseline expression in cell lines and tumours were calculated. We found these to be highly similar across all samples with most similarity found within a given sample type. Integration of proteomics and transcriptomics data showed median correlation across cell lines to be 0.58 (range between 0.43 and 0.66). Additionally, in agreement with previous studies, variation in mRNA levels was often a poor predictor of changes in protein abundance. To our knowledge, this work constitutes the first meta-analysis focusing on cancer-related public proteomics datasets. We therefore also highlight shortcomings and limitations of such studies. All data is available through PRIDE dataset identifier PXD013455 and in Expression Atlas.

scholarly journals MicroRNAs: Promising New Antiangiogenic Targets in Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sandra Gallach ◽  
Silvia Calabuig-Fariñas ◽  
Eloisa Jantus-Lewintre ◽  
Carlos Camps
Keyword(s):  
Cell Types ◽  
Biological Processes ◽  
Tumour Angiogenesis ◽  
Proliferation And Apoptosis ◽  
Sequence Complementarity ◽  
Specific Proteins ◽  
Health And Disease ◽  
Multiple Cell ◽  
Non Coding Rnas

MicroRNAs are one class of small, endogenous, non-coding RNAs that are approximately 22 nucleotides in length; they are very numerous, have been phylogenetically conserved, and involved in biological processes such as development, differentiation, cell proliferation, and apoptosis. MicroRNAs contribute to modulating the expression levels of specific proteins based on sequence complementarity with their target mRNA molecules and so they play a key role in both health and disease. Angiogenesis is the process of new blood vessel formation from preexisting ones, which is particularly relevant to cancer and its progression. Over the last few years, microRNAs have emerged as critical regulators of signalling pathways in multiple cell types including endothelial and perivascular cells. This review summarises the role of miRNAs in tumour angiogenesis and their potential implications as therapeutic targets in cancer.

scholarly journals An integrated landscape of protein expression in human cancer

2019 ◽  
Author(s):  
Andrew F. Jarnuczak ◽  
Hanna Najgebauer ◽  
Mitra Barzine ◽  
Deepti J. Kundu ◽  
Fatemeh Ghavidel ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Lines ◽  
Transcriptional Control ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protein Abundance ◽  
Mrna Levels ◽  
Future Studies ◽  
Poor Predictor ◽  
Transcriptomics Data

ABSTRACTUsing public proteomics datasets, mostly available through the PRIDE database, we assembled a proteomics resource for 191 cancer cell lines and 246 clinical tumour samples, across 13 cancer lineages. We found that baseline protein abundance in cell lines was generally representative of tumours. However, when considering differences in protein expression between tumour subtypes, as exemplified in the breast lineage, many of these changes were no longer recapitulated in the cell line models. Integration of proteomics and transcriptomics data suggested that the level of transcriptional control in cell lines changed significantly depending on their lineage. Additionally, in agreement with previous studies, variation in mRNA levels was often a poor predictor of changes in protein abundance. To our knowledge, this work constitutes the first meta-analysis study including cancer-related proteomics datasets. We anticipate this aggregated dataset will be of significant aid to future studies requiring a reference to baseline protein expression in cancer.

scholarly journals Metabolic Reprogramming in Metastatic Melanoma with Acquired Resistance to Targeted Therapies: Integrative Metabolomic and Proteomic Analysis

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1323
Author(s):  
Laura Soumoy ◽  
Corentin Schepkens ◽  
Mohammad Krayem ◽  
Ahmad Najem ◽  
Vanessa Tagliatti ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Cell Lines ◽  
1H Nmr ◽  
Acquired Resistance ◽  
Significant Proportion ◽  
Drug Efficacy ◽  
Protein Microarrays ◽  
Mapk Signaling ◽  
Metabolic Reprogramming ◽  
Cellular Mechanisms

Treatments of metastatic melanoma underwent an impressive development over the past few years, with the emergence of small molecule inhibitors targeting mutated proteins, such as BRAF, NRAS, or cKIT. However, since a significant proportion of patients acquire resistance to these therapies, new strategies are currently being considered to overcome this issue. For this purpose, melanoma cell lines with mutant BRAF, NRAS, or cKIT and with acquired resistances to BRAF, MEK, or cKIT inhibitors, respectively, were investigated using both 1H-NMR-based metabonomic and protein microarrays. The 1H-NMR profiles highlighted a similar go and return pattern in the metabolism of the BRAF, NRAS, and cKIT mutated cell lines. Indeed, melanoma cells exposed to mutation-specific inhibitors underwent metabolic disruptions following acute exposure but partially recovered their basal metabolism in long-term exposure, most likely acquiring resistance skills. The protein microarrays inquired about the potential cellular mechanisms used by the resistant cells to escape drug treatment, by showing decreased levels of proteins linked to the drug efficacy, especially in the downstream part of the MAPK signaling pathway. Integrating metabonomic and proteomic findings revealed some metabolic pathways (i.e., glutaminolysis, choline metabolism, glutathione production, glycolysis, oxidative phosphorylation) and key proteins (i.e., EPHA2, DUSP4, and HIF-1A) as potential targets to discard drug resistance.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals Plasma proteomics of green turtles (Chelonia mydas) reveals pathway shifts and potential biomarker candidates associated with health and disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
David P Marancik ◽  
Justin R Perrault ◽  
Lisa M Komoroske ◽  
Jamie A Stoll ◽  
Kristina N Kelley ◽  
...  
Keyword(s):  
Chelonia Mydas ◽  
Sea Turtle ◽  
Protein Abundance ◽  
Plasma Samples ◽  
Important Species ◽  
Green Turtles ◽  
Rehabilitation Programs ◽  
Potential Biomarker ◽  
Health And Disease

Abstract Evaluating sea turtle health can be challenging due to an incomplete understanding of pathophysiologic responses in these species. Proteome characterization of clinical plasma samples can provide insights into disease progression and prospective biomarker targets. A TMT-10-plex-LC–MS/MS platform was used to characterize the plasma proteome of five, juvenile, green turtles (Chelonia mydas) and compare qualitative and quantitative protein changes during moribund and recovered states. The 10 plasma samples yielded a total of 670 unique proteins. Using ≥1.2-fold change in protein abundance as a benchmark for physiologic upregulation or downregulation, 233 (34.8%) were differentially regulated in at least one turtle between moribund and recovered states. Forty-six proteins (6.9%) were differentially regulated in all five turtles with two proteins (0.3%) demonstrating a statistically significant change. A principle component analysis showed protein abundance loosely clustered between moribund samples or recovered samples and for turtles that presented with trauma (n = 3) or as intestinal floaters (n = 2). Gene Ontology terms demonstrated that moribund samples were represented by a higher number of proteins associated with blood coagulation, adaptive immune responses and acute phase response, while recovered turtle samples included a relatively higher number of proteins associated with metabolic processes and response to nutrients. Abundance levels of 48 proteins (7.2%) in moribund samples significantly correlated with total protein, albumin and/or globulin levels quantified by biochemical analysis. Differentially regulated proteins identified with immunologic and physiologic functions are discussed for their possible role in the green turtle pathophysiologic response and for their potential use as diagnostic biomarkers. These findings enhance our ability to interpret sea turtle health and further progress conservation, research and rehabilitation programs for these ecologically important species.

scholarly journals YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

2021 ◽  
Vol 22 (13) ◽  
pp. 7226
Author(s):  
Violeta Stojanovska ◽  
Aneri Shah ◽  
Katja Woidacki ◽  
Florence Fischer ◽  
Mario Bauer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cell Function ◽  
Trophoblast Cell ◽  
Mrna Levels ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Apoptosis And Inflammation

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.

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