Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 102
Filter
1.
Cells ; 11(22)2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2199805

ABSTRACT

Long Intergenic Non-Protein Coding RNA 665 (LINC00665) is an RNA gene located on the minus strand of chromosome 19. This lncRNA acts as a competing endogenous RNA for miR-4458, miR-379-5p, miR-551b-5p, miR-3619-5p, miR-424-5p, miR-9-5p, miR-214-3p, miR-126-5p, miR-149-3p, miR-379-5p, miR-665, miR-34a-5p, miR-186-5p, miR-138-5p, miR-181c-5p, miR-98, miR-195-5p, miR-224-5p, miR-3619, miR-708, miR-101, miR-1224-5p, miR-34a-5p, and miR-142-5p. Via influencing expression of these miRNAs, it can enhance expression of a number of oncogenes. Moreover, LINC00665 can influence activity of Wnt/ß-Catenin, TGF-ß, MAPK1, NF-κB, ERK, and PI3K/AKT signaling. Function of this lncRNA has been assessed through gain-of-function tests and/or loss-of-function studies. Furthermore, diverse research groups have evaluated its expression levels in tissue samples using microarray and RT-qPCR techniques. In this manuscript, we have summarized the results of these studies and categorized them in three sections, i.e., cell line studies, animal studies, and investigations in clinical samples.


Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Animals , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Phosphatidylinositol 3-Kinases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms/genetics , Signal Transduction/genetics
2.
Int J Mol Sci ; 23(15)2022 Aug 02.
Article in English | MEDLINE | ID: covidwho-1990297

ABSTRACT

The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers' choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.


Subject(s)
Communicable Diseases , Neoplasms , B-Lymphocytes , Communicable Diseases/genetics , High-Throughput Nucleotide Sequencing , Humans , Neoplasms/genetics , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes
3.
Patient Educ Couns ; 105(7): 2436-2442, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2150396

ABSTRACT

OBJECTIVES: Healthy individuals from hereditary cancer families undergoing genetic testing for cancer susceptibility (GTC) report more distress when they perceive their social support as low and suppress their emotions. This study aimed to explore how suppressing emotions and perceiving others as unsupportive are related with cancer-risk distress. METHODS: We performed a regression-based mediation analysis to assess if expressive suppression mediates or is mediated by perceived social support in the relation with cancer-risk distress. Participants were 125 healthy adults aged over 18 (M = 36.07, SD = 12.86), mostly female (72,4%), who undergone GTC to assess the presence of hereditary breast and ovarian cancer or Lynch syndromes. RESULTS: Controlling for age and gender, we found a moderate size indirect effect of social support on cancer-risk distress through expressive suppression (ß = -0.095) and a direct effect of expressive suppression on cancer-risk distress. CONCLUSIONS: When healthy individuals from hereditary cancer families perceive their social network as less responsive, they tend to not express their emotions, which relates to increased distress facing GTC. PRACTICE IMPLICATIONS: Practitioners may assess cancer-risk related distress before the GTC and offer distressed individuals interventions focused on changing emotion regulation strategies in a safe group context.


Subject(s)
Genetic Predisposition to Disease , Neoplasms , Adult , Emotions/physiology , Female , Health Status , Humans , Male , Neoplasms/genetics , Social Support
4.
J Interferon Cytokine Res ; 42(11): 592-593, 2022 11.
Article in English | MEDLINE | ID: covidwho-2117093

ABSTRACT

Recently, messenger ribonucleic acid (mRNA) vaccine research and development became a hotspot in the field of prevention and treatment of Corona Virus Disease 2019 (COVID-19) and some other disorders. mRNA vaccine shows many advantages over other vaccines, including cost-effectiveness, safety, and rapid optimization of antigen-specific sequences and shorter development cycle. Cancer progression is significantly associated with immune response, and mRNA vaccine also shows obvious advantages for cancer immunotherapy. In this study, we briefly summarize the recent advances and discuss the perspectives on tumor mRNA vaccine development; particularly, these findings pave an avenue for effective cancer prevention and treatment.


Subject(s)
COVID-19 , Cancer Vaccines , Neoplasms , Humans , COVID-19/prevention & control , Cancer Vaccines/genetics , Neoplasms/genetics , Neoplasms/prevention & control , RNA, Messenger/genetics
5.
Front Biosci (Landmark Ed) ; 27(9): 253, 2022 08 31.
Article in English | MEDLINE | ID: covidwho-2067594

ABSTRACT

SIRT1 was discovered in 1979 but growing interest in this protein occurred only 20 years later when its overexpression was reported to prolong the lifespan of yeast. Since then, several studies have shown the benefits of its increased expression in preventing or delaying of many diseases. SIRT1, as a histone deacetylase, is an epigenetic regulator but it has wide range of non-histone targets which are involved in metabolism, energy sensing pathways, circadian machinery and in inflammatory regulation. Disturbances in these interconnected processes cause different diseases, however it seems they have common roots in unbalanced inflammatory processes and lower level or inactivation of SIRT1. SIRT1 inactivation was implicated in coronavirus disease (COVID-19) severity as well and its low level counted as a predictor of uncontrolled COVID-19. Several other diseases such as metabolic disease, obesity, diabetes, Alzheimer's disease, cardiovascular disease or depression are related to chronic inflammation and similarly show decreased SIRT1 level. It has recently been known that SIRT1 is inducible by calorie restriction/proper diet, physical activity and appropriate emotional state. Indeed, a healthier metabolic state belongs to higher level of SIRT1 expression. These suggest that appropriate lifestyle as non-pharmacological treatment may be a beneficial tool in the prevention of inflammation or metabolic disturbance-related diseases as well as could be a part of the complementary therapy in medical practice to reach better therapeutic response and quality of life. We aimed in this review to link the beneficial effect of SIRT1 with those diseases, where its level decreased. Moreover, we aimed to collect evidences of interventions or treatments, which increase SIRT1 expression and thus, open the possibility to use them as preventive or complementary therapies in medical practice.


Subject(s)
Epigenesis, Genetic , Metabolic Diseases , Neoplasms , Sirtuin 1 , COVID-19 , Homeostasis , Humans , Inflammation , Metabolic Diseases/genetics , Metabolic Diseases/prevention & control , Neoplasms/genetics , Neoplasms/prevention & control , Quality of Life , Sirtuin 1/genetics , Sirtuin 1/metabolism
6.
Nat Rev Cancer ; 22(10): 550-556, 2022 10.
Article in English | MEDLINE | ID: covidwho-2050397
7.
Cell Death Dis ; 13(10): 846, 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2050337

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Of particular interest for this topic are the signaling cascades that regulate cell survival and death, two opposite cell programs whose control is hijacked by viral infections. The AKT and the Unfolded Protein Response (UPR) pathways, which maintain cell homeostasis by regulating these two programs, have been shown to be deregulated during SARS-CoVs infection as well as in the development of cancer, one of the most important comorbidities in relation to COVID-19. Recent evidence revealed two way crosstalk mechanisms between the AKT and the UPR pathways, suggesting that they might constitute a unified homeostatic control system. Here, we review the role of the AKT and UPR pathways and their interaction in relation to SARS-CoV-2 infection as well as in tumor onset and progression. Feedback regulation between AKT and UPR pathways emerges as a master control mechanism of cell decision making in terms of survival or death and therefore represents a key potential target for developing treatments for both viral infection and cancer. In particular, drug repositioning, the investigation of existing drugs for new therapeutic purposes, could significantly reduce time and costs compared to de novo drug discovery.


Subject(s)
COVID-19 , Neoplasms , Humans , Neoplasms/genetics , Proto-Oncogene Proteins c-akt , SARS-CoV-2 , Up-Regulation
8.
Lancet Oncol ; 23(10): e450-e458, 2022 10.
Article in English | MEDLINE | ID: covidwho-2042234

ABSTRACT

Years of research exploring mRNA vaccines for cancer treatment in preclinical and clinical trials have set the stage for the rapid development of mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and the inherent advantage in ease of production, which rivals the best available conventional vaccine manufacture methods, renders mRNA vaccines a promising option for cancer immunotherapy. Technological advances have optimised mRNA-based vaccine stability, structure, and delivery methods, and multiple clinical trials investigating mRNA vaccine therapy are now enrolling patients with various cancer diagnoses. Although therapeutic mRNA-based cancer vaccines have not yet been approved for standard treatment, encouraging results from early clinical trials with mRNA vaccines as monotherapy and in combination with checkpoint inhibitors have been obtained. This Review summarises the latest clinical advances in mRNA-based vaccines for cancer treatment and reflects on future perspectives and challenges for this new and promising treatment approach.


Subject(s)
Cancer Vaccines , Neoplasms , Cancer Vaccines/adverse effects , Humans , Neoplasms/genetics , Neoplasms/therapy , Pandemics , RNA, Messenger/genetics , Vaccines, Synthetic , mRNA Vaccines
9.
Signal Transduct Target Ther ; 7(1): 300, 2022 08 30.
Article in English | MEDLINE | ID: covidwho-2031821

ABSTRACT

Ubiquitination is a highly conserved and fundamental posttranslational modification (PTM) in all eukaryotes regulating thousands of proteins. The RING (really interesting new gene) finger (RNF) protein, containing the RING domain, exerts E3 ubiquitin ligase that mediates the covalent attachment of ubiquitin (Ub) to target proteins. Multiple reviews have summarized the critical roles of the tripartite-motif (TRIM) protein family, a subgroup of RNF proteins, in various diseases, including cancer, inflammatory, infectious, and neuropsychiatric disorders. Except for TRIMs, since numerous studies over the past decades have delineated that other RNF proteins also exert widespread involvement in several diseases, their importance should not be underestimated. This review summarizes the potential contribution of dysregulated RNF proteins, except for TRIMs, to the pathogenesis of some diseases, including cancer, autoimmune diseases, and neurodegenerative disorder. Since viral infection is broadly involved in the induction and development of those diseases, this manuscript also highlights the regulatory roles of RNF proteins, excluding TRIMs, in the antiviral immune responses. In addition, we further discuss the potential intervention strategies targeting other RNF proteins for the prevention and therapeutics of those human diseases.


Subject(s)
Neoplasms , Ubiquitin-Protein Ligases , Humans , Neoplasms/genetics , Tripartite Motif Proteins/genetics , Tripartite Motif Proteins/metabolism , Ubiquitin/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitination/genetics
10.
Nat Med ; 28(9): 1750, 2022 09.
Article in English | MEDLINE | ID: covidwho-2028686
12.
Int J Mol Sci ; 23(16)2022 Aug 19.
Article in English | MEDLINE | ID: covidwho-1997644

ABSTRACT

Cyclophilin A (CypA), which has peptidyl-prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.


Subject(s)
Cyclophilin A , Neoplasms , Basigin/genetics , Basigin/metabolism , Cyclophilin A/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Signal Transduction
13.
Math Biosci Eng ; 19(11): 11172-11194, 2022 08 04.
Article in English | MEDLINE | ID: covidwho-1997893

ABSTRACT

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), also known as COVID-19, is currently prevalent worldwide and poses a significant threat to human health. Individuals with cancer may have an elevated risk for SARS-CoV-2 infections and adverse outcomes. Therefore, it is necessary to explore the internal relationship between these two diseases. In this study, transcriptome analyses were performed to detect mutual pathways and molecular biomarkers in three types of common cancers of the breast, liver, colon, and COVID-19. Such analyses could offer a valuable understanding of the association between COVID-19 and cancer patients. In an analysis of RNA sequencing datasets for three types of cancers and COVID-19, we identified a sum of 38 common differentially expressed genes (DEGs). A variety of combinational statistical approaches and bioinformatics techniques were utilized to generate the protein-protein interaction (PPI) network. Subsequently, hub genes and critical modules were found using this network. In addition, a functional analysis was conducted using ontologies keywords, and pathway analysis was also performed. Some common associations between cancer and the risk and prognosis of COVID-19 were discovered. The datasets also revealed transcriptional factors-gene interplay, protein-drug interaction, and a DEGs-miRNAs coregulatory network with common DEGs. The potential medications discovered in this investigation could be useful in treating cancer and COVID-19.


Subject(s)
COVID-19 , MicroRNAs , Neoplasms , COVID-19/epidemiology , Computational Biology/methods , Humans , Neoplasms/epidemiology , Neoplasms/genetics , SARS-CoV-2
14.
Int J Mol Sci ; 23(15)2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1994080

ABSTRACT

Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/ß-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.


Subject(s)
Flavanones , MicroRNAs , Neoplasms , Animals , Carcinogenesis , Flavanones/pharmacology , Flavanones/therapeutic use , Mice , MicroRNAs/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Signal Transduction
15.
Nat Commun ; 13(1): 4678, 2022 08 09.
Article in English | MEDLINE | ID: covidwho-1984385

ABSTRACT

There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling.


Subject(s)
COVID-19 , Neoplasms , COVID-19/genetics , Computational Biology , Humans , Neoplasms/genetics , Software , Transcriptome , Workflow
16.
Gene ; 840: 146772, 2022 Oct 05.
Article in English | MEDLINE | ID: covidwho-1983092

ABSTRACT

The expression of ULK1, a core protein of autophagy, is closely related to autophagic activity. Numerous studies have shown that pathological abnormal expression of ULK1 is associated with various human diseases such as neurological disorders, infections, cardiovascular diseases, liver diseases and cancers. In addition, new advances in the regulation of ULK1 have been identified. Furthermore, targeting ULK1 as a therapeutic strategy for diseases is gaining attention as new corresponding activators or inhibitors are being developed. In this review, we describe the structure and regulation of ULK1 as well as the current targeted activators and inhibitors. Moreover, we highlight the pathological disorders of ULK1 expression and its critical role in human diseases.


Subject(s)
Autophagy-Related Protein-1 Homolog/metabolism , Autophagy , Intracellular Signaling Peptides and Proteins/metabolism , Neoplasms , Autophagy/physiology , Autophagy-Related Protein-1 Homolog/chemistry , Autophagy-Related Protein-1 Homolog/genetics , Humans , Intracellular Signaling Peptides and Proteins/chemistry , Intracellular Signaling Peptides and Proteins/genetics , Neoplasms/genetics
19.
Nat Med ; 28(7): 1345-1347, 2022 07.
Article in English | MEDLINE | ID: covidwho-1972636
20.
Cells ; 11(15)2022 07 23.
Article in English | MEDLINE | ID: covidwho-1957237

ABSTRACT

Coronavirus disease (COVID-19) is an infectious disease that is caused by a highly contagious and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). This infection started to spread across the world in 2019 and rapidly turned into a global pandemic, causing an urgent necessity for treatment strategies development. The mRNA vaccines against SARS-CoV-2 can trigger an immune response, providing genetic information that allows the production of spike glycoproteins. MiRNAs play a crucial role in diverse key cellular processes, including antiviral defense. Several miRNAs are described as key factors in SARS-CoV-2 human infection through the regulation of ACE2 levels and by the inhibition of SARS-CoV-2 replication and spike expression. Consequently, these molecules have been considered as highly promising biomarkers. In numerous human malignancies, it has been recognized that miRNAs expression is dysregulated. Since miRNAs can target SARS-CoV-2-associated mRNAs, in cancer patients, the deregulation of these molecules can impair the immune response to the vaccines. Therefore, in this review, we propose a miRNA profile of seven SARS-CoV-2-related miRNAs, namely miR-214, miR-98-5p, miR-7-5p, miR-24-3p, miR-145-5p, miR-223-3p and miR-15b-5p, that are deregulated in a high number of cancers and have the potential to be used as prognostic biomarkers to stratify cancer patients.


Subject(s)
COVID-19 , MicroRNAs , Neoplasms , COVID-19 Vaccines , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms/genetics , RNA, Messenger/genetics , SARS-CoV-2 , Vaccination
SELECTION OF CITATIONS
SEARCH DETAIL